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1.
BMC Pregnancy Childbirth ; 23(1): 207, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-36973793

ABSTRACT

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.


Subject(s)
Pregnancy Complications, Infectious , Premature Birth , Streptococcal Infections , Infant, Newborn , Pregnancy , Female , Humans , Adult , Antibiotic Prophylaxis , Retrospective Studies , Streptococcus agalactiae , Infectious Disease Transmission, Vertical/prevention & control , Anti-Bacterial Agents/therapeutic use , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , Risk Factors , Pregnancy, Multiple , Streptococcal Infections/epidemiology , Streptococcal Infections/prevention & control , Streptococcal Infections/diagnosis , Premature Birth/drug therapy
2.
J Environ Manage ; 336: 117654, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-36870320

ABSTRACT

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 (∼2-3 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 (∼<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.


Subject(s)
Groundwater , Lakes , Rivers , China , Hydrology
3.
Angew Chem Int Ed Engl ; 62(8): e202214391, 2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36420911

ABSTRACT

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.

4.
J Am Chem Soc ; 144(7): 3083-3090, 2022 Feb 23.
Article in English | MEDLINE | ID: mdl-35138088

ABSTRACT

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.

5.
J Environ Manage ; 321: 115960, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36104881

ABSTRACT

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.


Subject(s)
Geology , Sand , Facies , Humans , Water , Water Wells
6.
J Neuroinflammation ; 15(1): 15, 2018 Jan 12.
Article in English | MEDLINE | ID: mdl-29329580

ABSTRACT

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.


Subject(s)
Apoptosis/physiology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Retinal Pigment Epithelium/cytology , Retinal Pigment Epithelium/metabolism , Animals , Female , Pyroptosis/physiology , Rats , Rats, Long-Evans , Rodentia , Signal Transduction/physiology , Vitreous Body/cytology , Vitreous Body/metabolism
7.
Lipids Health Dis ; 17(1): 3, 2018 Jan 04.
Article in English | MEDLINE | ID: mdl-29301530

ABSTRACT

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.


Subject(s)
Alzheimer Disease/pathology , Atherosclerosis/pathology , Glomerulonephritis/pathology , Lipid Metabolism/immunology , Macular Degeneration/pathology , Alzheimer Disease/genetics , Alzheimer Disease/immunology , Alzheimer Disease/metabolism , Animals , Apolipoproteins/genetics , Apolipoproteins/immunology , Atherosclerosis/genetics , Atherosclerosis/immunology , Atherosclerosis/metabolism , Cholesterol/metabolism , Complement Activation , Complement System Proteins/genetics , Complement System Proteins/immunology , Gene Expression , Genetic Variation , Glomerulonephritis/genetics , Glomerulonephritis/immunology , Glomerulonephritis/metabolism , Humans , Inflammation , Lipid Metabolism/genetics , Macrophages/immunology , Macrophages/pathology , Macular Degeneration/genetics , Macular Degeneration/immunology , Macular Degeneration/metabolism , Oxidative Stress
8.
J Am Chem Soc ; 139(46): 16482-16485, 2017 11 22.
Article in English | MEDLINE | ID: mdl-29083177

ABSTRACT

Pollutant treatment is critical in modern society and often requires tedious workup and expensive facilities. By virtue of structural diversity and tunability, metal-organic frameworks (MOFs) have shown promise in pollutant control. We herein report a powerful templated freeze-drying protocol for the fabrication of multifunctional MOF hollow tubular structures for both air and liquid contaminants filtration. Various hollow tube systems (e.g., "Janus", "coaxial" and "cellular") are produced. Specially, a multilayer coaxial MOF hollow tube is prepared for highly efficient capture of mixed inorganic-organic liquid contaminants with >94% filtration efficiency. Further, a "cellular" hollow tube with low pressure-drop (12 Pa, 10 cm s-1) is applied in particulate matter filtration with high efficiency (>92%). Given the rich structural and functional diversities, this protocol might bring MOFs into industrial applications to remediate environmental problems.


Subject(s)
Environmental Pollutants/analysis , Organometallic Compounds/chemistry , Environmental Monitoring , Porosity , Surface Properties
9.
Glia ; 64(5): 716-29, 2016 May.
Article in English | MEDLINE | ID: mdl-26711882

ABSTRACT

Understanding retinal vascular development is crucial because many retinal vascular diseases such as diabetic retinopathy (in adults) or retinopathy of prematurity (in children) are among the leading causes of blindness. Given the localization of the protein Dp71 around the retinal vessels in adult mice and its role in maintaining retinal homeostasis, the aim of this study was to determine if Dp71 was involved in astrocyte and vascular development regulation. An experimental study in mouse retinas was conducted. Using a dual immunolabeling with antibodies to Dp71 and anti-GFAP for astrocytes on retinal sections and isolated astrocytes, it was found that Dp71 was expressed in wild-type (WT) mouse astrocytes from early developmental stages to adult stage. In Dp71-null mice, a reduction in GFAP-immunopositive astrocytes was observed as early as postnatal day 6 (P6) compared with WT mice. Using real-time PCR, it was showed that Dp71 mRNA was stable between P1 and P6, in parallel with post-natal vascular development. Regarding morphology in Dp71-null and WT mice, a significant decrease in overall astrocyte process number in Dp71-null retinas at P6 to adult age was found. Using fluorescence-conjugated isolectin Griffonia simplicifolia on whole mount retinas, subsequent delay of developing vascular network at the same age in Dp71-null mice was found. An evidence that the Dystrophin Dp71, a membrane-associated cytoskeletal protein and one of the smaller Duchenne muscular dystrophy gene products, regulates astrocyte morphology and density and is associated with subsequent normal blood vessel development was provided.


Subject(s)
Astrocytes/cytology , Dystrophin/deficiency , Gene Expression Regulation/genetics , Retina/cytology , Retinal Vessels/anatomy & histology , Age Factors , Animals , Animals, Newborn , Astrocytes/metabolism , Cadherins/antagonists & inhibitors , Cadherins/genetics , Cadherins/metabolism , Cell Count , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Dystrophin/genetics , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , In Vitro Techniques , Mice , Mice, Inbred C57BL , Mice, Knockout , RNA, Messenger , Retinal Vessels/metabolism , Statistics, Nonparametric , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
10.
J Am Chem Soc ; 138(34): 10810-3, 2016 08 31.
Article in English | MEDLINE | ID: mdl-27511140

ABSTRACT

The applications of metal-organic frameworks (MOFs) toward industrial separation, catalysis, sensing, and some sophisticated devices are drastically affected by their intrinsic fragility and poor processability. Unlike organic polymers, MOF crystals are insoluble in any solvents and are usually not thermoplastic, which means traditional solvent- or melting-based processing techniques are not applicable for MOFs. Herein, a continuous phase transformation processing strategy is proposed for fabricating and shaping MOFs into processable fluids, shaped bodies, and even MOF foams that are capable of reversible transformation among these states. Based on this strategy, a cup-shaped Cu-MOF composite and hierarchically porous MOF foam were developed for highly efficient catalytic C-H oxidation (conv. 76% and sele. 93% for cup-shaped Cu-MOF composite and conv. 92% and sele. 97% for porous foam) with ease of recycling and dramatically improved kinetics. Furthermore, various MOF-based foams with low densities (<0.1 g cm(-3)) and high MOF loadings (up to 80 wt %) were obtained via this protocol. Imparted with hierarchically porous structures and fully accessible MOFs uniformly distributed, these foams presented low energy penalty (pressure drop <20 Pa, at 500 mL min(-1)) and showed potential applications as efficient membrane reactors.

11.
J Neuroinflammation ; 12: 121, 2015 Jun 24.
Article in English | MEDLINE | ID: mdl-26104676

ABSTRACT

BACKGROUND: The membrane attack complex (MAC) is a key player in the pathogenesis of age-related macular degeneration (AMD) and is a putative activator of the NLRP3 inflammasome. Amyloid beta (Aß), a component of drusen deposits, has also been implicated in inflammasome activation by our work and those of others. However, the interactions of MAC and Aß are still poorly understood, especially their roles in aging and retinal degenerative pathologies. Since inflammasome activation may represent a key cellular pathway underlying age-related chronic inflammation in the eye, the purpose of this study is to identify the effects associated with MAC and inflammasome activation in the retinal pigment epithelium (RPE)/choroid and to evaluate the therapeutic merits of MAC suppression. METHODS: Adult Long-Evans rats were divided into treatment and control groups. Treatment groups received oral aurin tricarboxylic acid complex (ATAC), a MAC inhibitor, in drinking-water, and control groups received drinking-water alone (No ATAC). Groups were sacrificed at 7.5 or 11.5 months, after approximately 40 days of ATAC treatment. To study age-related changes of Aß and MAC in RPE/choroid, naive animals were sacrificed at 2.5, 7.5, and 11.5 months. Eye tissues underwent immunohistochemistry and western blot analysis for MAC, Aß, NF-κB activation, as well as cleaved caspase-1 and IL-18. Vitreal samples were collected and assessed by multiplex assays for secreted levels of IL-18 and IL-1ß. Statistical analyses were performed, and significance level was set at p ≤ 0.05. RESULTS: In vivo studies demonstrated an age-dependent increase in MAC, Aß, and NF-κB activation in the RPE/choroid. Systemic ATAC resulted in a prominent reduction in MAC formation and a concomitant reduction in inflammasome activation measured by cleaved caspase-1 and secreted levels of IL-18 and IL-1ß, but not in NF-κB activation. In vitro studies demonstrated Aß-induced MAC formation on RPE cells. CONCLUSIONS: Age-dependent increases in Aß and MAC are present in the rodent outer retina. Our results suggest that suppressing MAC formation and subsequent inflammasome activation in the RPE/choroid may reduce chronic low-grade inflammation associated with IL-18 and IL-1ß in the outer retina.


Subject(s)
Aging/metabolism , Amyloid beta-Peptides/metabolism , Carrier Proteins/metabolism , Choroid/metabolism , Complement Membrane Attack Complex/metabolism , Inflammasomes/metabolism , Retina/metabolism , Animals , Aurintricarboxylic Acid/pharmacology , Choroid/drug effects , Disease Models, Animal , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Macular Degeneration/metabolism , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Rats , Rats, Long-Evans , Retina/drug effects
12.
Mol Vis ; 21: 264-72, 2015.
Article in English | MEDLINE | ID: mdl-25814824

ABSTRACT

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people 50 years of age or older in developed countries. The homozygous CC genotype in the complement factor H (CFH) Y402H single nucleotide polymorphism (SNP; rs1061170) is widely recognized as a risk factor for the development of AMD. In this study, we examined vitreal levels of granulocyte macrophage colony-stimulating factor (GM-CSF), a hematopoietic cytokine, and macrophages in the choroid of postmortem human eyes genotyped for the CFH Y402H SNP. METHODS: Twenty-two pairs of postmortem, non-diseased, human donor eyes were obtained. The vitreous and retinal tissues of the left eyes were collected for GM-CSF level measurement and CFH Y402H genotyping, respectively. The right eyes were paraffin-embedded and sectioned for immunohistochemistry using a macrophage and microglia marker, CD68. Cell cultures of RPE cells were stimulated with complement C3a, C5a, 4-hydroxynonenal (HNE), or tumor necrosis factor alpha (TNF-α), and GM-CSF expression was measured with a suspension assay or quantitative PCR. RESULTS: Eyes genotyped with the CC or the CT risk variant of the CFH Y402H SNP showed significantly increased levels of GM-CSF in the vitreous compared to eyes with the protective TT variant (mean ± standard error of mean, 607.54±85.83 pg/ml or 656.32±15.20 pg/ml versus 286.69±81.96 pg/ml, p<0.05). The choroid of eye tissues genotyped with the CC variant showed higher levels of CD68 immunoreactivity than the tissues genotyped with the TT variant (p<0.05). The GM-CSF levels detected in the supernatant of RPE cells in culture treated with HNE or TNF-α were significantly higher compared to the non-treated control (145.88±5.06 pg/ml and 149.32±3.76 pg/ml versus 123.27±4.05 pg/ml, p<0.05). Furthermore, the gene expression of GM-CSF detected in the lysate of RPE cells stimulated with complement C3a or C5a showed significantly increased fold changes compared to the non-treated control (C3a: 2.38±0.31 fold, p<0.05; C5a: 2.84±0.54 fold, p<0.01). CONCLUSIONS: Our data showed a relationship between the CFH Y402H polymorphism and GM-CSF levels in the vitreous and accumulation of choroidal macrophages in the postmortem eye. These data suggest that the at-risk variant of the CFH gene may contribute to the dysregulation of proinflammatory cytokines locally in the eye.


Subject(s)
Choroid/metabolism , Complement Factor H/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Macrophages/cytology , Polymorphism, Single Nucleotide , Vitreous Body/metabolism , Aldehydes/pharmacology , Amino Acid Substitution , Autopsy , Cells, Cultured , Choroid/chemistry , Choroid/cytology , Complement C3a/pharmacology , Complement C5a/pharmacology , Complement Factor H/metabolism , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Gene Expression , Genotype , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Macrophages/metabolism , Male , Middle Aged , Retinal Pigment Epithelium/cytology , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Vitreous Body/chemistry , Vitreous Body/cytology
13.
Mediators Inflamm ; 2015: 690243, 2015.
Article in English | MEDLINE | ID: mdl-25698849

ABSTRACT

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.


Subject(s)
Carrier Proteins/metabolism , Inflammasomes/metabolism , Macular Degeneration/metabolism , Animals , Bruch Membrane/metabolism , Bruch Membrane/pathology , Humans , Macular Degeneration/pathology , NLR Family, Pyrin Domain-Containing 3 Protein , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology
14.
Exp Eye Res ; 127: 49-58, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25041941

ABSTRACT

Chronic inflammation is a key pathogenic process in age-related macular degeneration (AMD). Amyloid-beta (Aß) is a constituent of AMD drusen and promotes the activation of NLRP3 inflammasome which facilitates the production of cytokines. We investigated the role of transcription factor NF-κB in the activation of inflammasome in the RPE and the effect of vinpocetine, a dietary supplement with inhibitory effect on NF-κΒ. ARPE19/NF-κB-luciferase reporter cells treated with Aß demonstrated enhanced NF-κB activation that was significantly suppressed by vinpocetine. Intraperitoneal injection of vinpocetine (15 mg/kg) inhibited NF-κB nuclear translocation and reduced the expression and activation of NLRP3, caspase-1, IL-1ß, IL-18, and TNF-α in the RPE of adult rats that received intraocular Αß, as measured by retinal immunohistochemistry and Western blot. Cytokine level in the vitreous was assayed using multiplex suspension arrays and revealed significantly lower concentration of MIP-3α, IL-6, IL-1α, IL-1ß, IL-18, and TNF-α in vinpocetine treated animals. These results suggest that the NF-κB pathway is activated by Aß in the RPE and signals the priming of NLRP3 inflammasome and the expression of pro-inflammatory cytokines including the inflammasome substrates IL-1ß and IL-18. NF-κB inhibition may be an effective approach to stem the chronic inflammatory milieu that underlies the development of AMD. Vinpocetine is a potentially useful anti-inflammatory agent that is well-tolerated in long term use.


Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Cytokines/metabolism , Inflammasomes/metabolism , NF-kappa B/metabolism , Retinal Pigment Epithelium/drug effects , Vasodilator Agents/pharmacology , Vinca Alkaloids/pharmacology , Amyloid beta-Peptides/pharmacology , Animals , Blotting, Western , Carrier Proteins , Cell Line , Enzyme-Linked Immunosorbent Assay , Female , Humans , Injections, Intraperitoneal , NLR Family, Pyrin Domain-Containing 3 Protein , Rats , Rats, Long-Evans , Receptors, Cytoplasmic and Nuclear/metabolism , Retinal Pigment Epithelium/metabolism , Vitreous Body/metabolism
15.
Mol Vis ; 19: 718-28, 2013.
Article in English | MEDLINE | ID: mdl-23559866

ABSTRACT

PURPOSE: Age-related macular degeneration (AMD) is a local, chronic inflammatory disease of the eye that is influenced by oxidative stress and dysregulation of the retinal pigment epithelium (RPE) associated with aging. The purpose of this study is to characterize the effects of oxidative stress and replicative senescence on the secreted cytokine profiles of RPE in vitro. METHODS: We used multiple, serial passages of human RPE cells from primary culture as an in vitro model of aging. Responses of early passage 5 (P5) and late passage 21 (P21) RPE cells were compared. Oxidative stress was induced in RPE cells (P5) by exposure to 75 µM hydroquinone (HQ) for 24 h. The secretome profiles of the RPE cells were measured with a multiplex suspension assay that assayed human cytokine, chemokine, and growth factors. Immunohistochemistry on younger (≤55 years old) and older (≥70 years old) human post-mortem donor eyes was used to verify selected cytokines. RESULTS: Supernatant of HQ-treated RPE cultures exhibited increased secreted levels of vascular endothelial growth factor (VEGF), interleukin (IL)-12, and IL-10 that reached statistical significance (p<0.05). Supernatant of late passage P21 RPE cultures exhibited decreased secreted levels of stromal cell-derived factor (SDF)-1α, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-8, IL-15, IL-6, and an increased level of IL-1ra compared to early passage P5 RPE cultures that reached statistical significance (p<0.05). Immunohistochemical analysis demonstrated increased expression of IL-1ra in RPE cells from older post-mortem donor eyes (≥70 years old) versus younger eyes (≤55 years old). CONCLUSIONS: Our data demonstrate a unique cytokine secretion profile of primary culture RPE cells at early and late passage. Our in vitro data suggest an age-specific modulation of cytokine secretion in RPE and is consistent with immunohistochemical analysis on post-mortem eyes. The secretion profile associated with RPE under conditions that mimic oxidative stress, another factor associated with the pathogenesis of AMD, emphasizes upregulation of the angiogenic growth factor, vascular endothelial growth factor. Together, these data support the role of advanced age and oxidative stress in inflammatory cytokine modulation in RPE cells.


Subject(s)
Cellular Senescence/drug effects , Cytokines/metabolism , Oxidants/toxicity , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Adult , Aged , Aged, 80 and over , Cell Death/drug effects , Cell Survival/drug effects , Cells, Cultured , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , Hydroquinones/toxicity , Interleukin 1 Receptor Antagonist Protein/metabolism , Male , Middle Aged , Models, Biological , Retinal Pigment Epithelium/drug effects
16.
Cytokine ; 62(3): 369-81, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23601964

ABSTRACT

Age related macular degeneration (AMD) is one of the leading causes of blindness in Western society. A hallmark of early stage AMD are drusen, extracellular deposits that accumulate in the outer retina. Advanced glycation endproducts (AGE) accumulate with aging and are linked to several age-related diseases such as Alzheimer's disease, osteoarthritis, atherosclerosis and AMD. AGE deposits are found in drusen and in Bruch's membrane of the eye and several studies have suggested its role in promoting oxidative stress, apoptosis and lipofuscin accumulation. Recently, complement activation and chronic inflammation have been implicated in the pathogenesis of AMD. While AGEs have been shown to promote inflammation in other diseases, whether it plays a similar role in AMD is not known. This study investigates the effects of AGE stimulation on pro- and anti-inflammatory pathways in primary culture of human retinal pigment epithelial cells (RPE). Differential gene expression studies revealed a total of 41 up- and 18 down-regulated RPE genes in response to AGE stimulation. These genes fell into three categories as assessed by gene set enrichment analysis (GSEA). The main categories were inflammation (interferon-induced, immune response) and proteasome degradation, followed by caspase signaling. Using suspension array technology, protein levels of secreted cytokines and growth factors were also examined. Anti-inflammatory cytokines including IL10, IL1ra and IL9 were all overexpressed. Pro-inflammatory cytokines including IL4, IL15 and IFN-γ were overexpressed, while other pro-inflammatory cytokines including IL8, MCP1, IP10 were underexpressed after AGE stimulation, suggesting a para-inflammation state of the RPE under these conditions. Levels of mRNA of chemokine, CXCL11, and viperin, RSAD2, were up-regulated and may play a role in driving the inflammatory response via the NF-kB and JAK-STAT pathways. CXCL11 was strongly immunoreactive and associated with drusen in the AMD eye. The pathways and novel genes identified here highlight inflammation as a key response to AGE stimulation in primary culture of human RPE, and identify chemokine CXCL11 as putative novel agent associated with the pathogenesis of AMD.


Subject(s)
Glycation End Products, Advanced/pharmacology , Inflammation/pathology , Macular Degeneration/pathology , Pigment Epithelium of Eye/pathology , Cell Survival/drug effects , Cells, Cultured , Chemokine CXCL11/metabolism , Down-Regulation/drug effects , Down-Regulation/genetics , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Inflammation/complications , Inflammation/genetics , Keratins/metabolism , Lysine/analogs & derivatives , Lysine/metabolism , Macular Degeneration/complications , Macular Degeneration/genetics , Pigment Epithelium of Eye/drug effects , Pigment Epithelium of Eye/metabolism , Postmortem Changes , Reproducibility of Results , Retinal Drusen/complications , Retinal Drusen/genetics , Retinal Drusen/pathology , Serum Albumin, Bovine/pharmacology , Tissue Donors , Up-Regulation/drug effects , Up-Regulation/genetics
17.
Retina ; 33(5): 1005-10, 2013 May.
Article in English | MEDLINE | ID: mdl-23474546

ABSTRACT

PURPOSE: Spectral domain optical coherence tomography can be used to measure both choroidal thickness and drusen load. The authors conducted an exploratory study using spectral domain optical coherence tomography to determine if a correlation between choroidal thickness and drusen load exists in patients with dry age-related macular degeneration. METHODS: Forty-four patients with dry age-related macular degeneration were recruited. The drusen area and volume were determined using the automated software algorithm of the spectral domain optical coherence tomography device, and choroidal thickness was measured using enhanced depth imaging. Correlations were determined using multivariable and univariable analyses. RESULTS: The authors found an inverse correlation between choroidal thickness and drusen load (r = -0.35, P = 0.04). Drusen load was also correlated with visual acuity (r = 0.32, P = 0.04). A correlation between choroidal thickness and visual acuity was suggested (r = -0.22, P = 0.21). CONCLUSION: Spectral domain optical coherence tomography can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. The measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for patients with dry age-related macular degeneration.


Subject(s)
Choroid/pathology , Macular Degeneration/pathology , Retinal Drusen/pathology , Tomography, Optical Coherence , Aged , Aged, 80 and over , Algorithms , Female , Humans , Macular Degeneration/physiopathology , Male , Middle Aged , Tomography, Optical Coherence/methods , Visual Acuity/physiology
18.
Glob Chall ; 7(7): 2300005, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37483418

ABSTRACT

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.

19.
Int J Biol Macromol ; 253(Pt 1): 126487, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37657312

ABSTRACT

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.


Subject(s)
Magnesium , Muramidase , Ovalbumin/chemistry , Muramidase/chemistry , Thermodynamics , Ions
20.
Int J Biol Macromol ; 253(Pt 2): 126759, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37678696

ABSTRACT

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.


Subject(s)
Erythritol , Sucrose , Kinetics , Sweetening Agents/analysis , Sugars , Digestion
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