Dysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age-related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive.
View Article and Find Full Text PDFSubretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A).
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
October 2024
Injuries to the retinal pigment epithelium (RPE) trigger immune responses, orchestrating interactions within the innate and adaptive immune systems in the outer retina and choroid. We previously reported that interleukin 17 (IL-17) is a pivotal signaling molecule originating from choroidal γδ T cells, exerting protective effects by mediating functional connections between the RPE and subretinal microglia. In this current study, we generated mice with aryl hydrocarbon receptor (AhR) knockout specifically in IL-17-producing cells.
View Article and Find Full Text PDFSteviol glycosides (SGs) are a natural sweetener widely used in the food and beverage industry, but the low solubility and stability of SG aqueous solutions greatly limit their application performance, especially in liquid formulations. In this work, we explore the solubility behavior of rebaudioside A (Reb A) in water, a major component of SGs, with the aim of clarifying the underlying mechanisms of the solubility and stability constraints of SGs, as well as the impact on their multifunctional properties. We demonstrate for the first time that Reb A exhibits hierarchical self-assembly in solutions, forming spherical micelles first when the concentration exceeds its critical micelle concentration (5.
View Article and Find Full Text PDFWe develop a novel hierarchically structured hydrogel by the supramolecular self-assembly of all-natural food-grade building blocks, glycyrrhizic acid (GA) and carrageenan (CG). The co-assembled GA-CG hydrogel system displays an unusual structural transition with the appearance from opacity to translucence and then to opacity, as a function of the concentration of metal ions. The unique GA-CG supramolecular hydrogel system can serve as solid, edible, and responsive active cargo delivery platforms for food and biomedical applications.
View Article and Find Full Text PDFGlycyrrhizic acid (GA), a naturally derived food-grade saponin molecule, is a promising alternative to synthetic surfactants for stabilizing multiphase systems including emulsions and foams, due to its biological activity and surface-active properties. Understanding the interfacial behavior of GA, particularly in relation to its complex self-assembly behaviors in water induced by multiple environmental stimuli, is crucial to its application in multiphase systems. In this study, we comprehensively investigate the interfacial structure and rheological properties of GA systems, as a function of pH and temperature, through Langmuir-Blodgett films combined with atomic force microscopy, interfacial particle tracking, adsorption kinetics, stress-relaxation behavior and interfacial dilatational rheology.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2023
Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury.
View Article and Find Full Text PDFThe re-emergence of Zika virus (ZIKV) remains a major public health threat that has raised worldwide attention. Accumulating evidence suggests that ZIKV can cause serious pathological changes to the human nervous system, including microcephaly in newborns. Recent studies suggest that metformin, an established treatment for diabetes may play a role in viral infection; however, little is known about the interactions between ZIKV infection and metformin administration.
View Article and Find Full Text PDFPolyphenols are frequently utilized antioxidants in active packaging and anti-immflamotary bioactives in tissue engineering. Herein, we introduced a novel method for the rapid (<5 s) fabrication of interfacial self-assembled zein films (ZF) at the air-water interface. Polyphenols with different partition coeffient (Log P), namely, curcumin, resveratrol, and quercetin, were simultaneously loaded during the laterally occurred self-assembly process of zein molecules, respectively.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2022
In ischemic retinopathy, overactivated retinal myeloid cells are a crucial driving force of pathological angiogenesis and inflammation. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) signaling are key regulators of inflammation. This study aims to investigate the association of cGAS-STING signaling with ischemic retinopathy and the regulation of its activation.
View Article and Find Full Text PDFACS Appl Mater Interfaces
October 2022
Artificial recapitulation of hierarchically porous films gained great interest due to their versatile functionalities and applications. However, the development of novel eco-friendly and nontoxic biopolymer-based porous films is still limited by the time-consuming fabrication processes and toxic organic reagents involved. Here, we reported a novel approach to rapidly (within 5 s) fabricate biopolymer-based hierarchically porous films via inducing the laterally occurring interfacial self-assembly of prolamins at the air-liquid interface during an antisolvent dripping procedure.
View Article and Find Full Text PDFFood packaging is a coordinated system comprising food processing, protection from contamination and adulteration, transportation and storage, and distribution and consumption at optimal cost with a minimum environmental impact to the packed food commodity. Active packaging involves deliberate addition of the functional ingredients either in the film or the package headspace to preserve the food quality, improve safety and nutrition aspects, and enhance the shelf-life. In this review, recent advances in the fabrication of biopolymer-based films, their classification (biodegradable-, active-, and intelligent packaging films), advanced fabrication strategies (composite-, multilayer-, and emulsified films), and special functions induced by the biopolymers to the film matrix (mechanical-, water resistance and gas barrier-, and optical properties, and bioactive compounds reservoir) were briefly discussed.
View Article and Find Full Text PDFProlamins are a group of storage proteins (zeins, kafirins, hordeins, secalins, gliadins, glutenins, and avenins) found in the endosperm of cereal grains and characterized by high glutamine and proline content. With the high proportion of nonpolar amino acids (40-80%) and peculiar solubility (alcohol (60-90%), acetic acid, and alkaline solutions), prolamins exhibit tunable self-assembly behaviors. In recent years, research practices of utilizing prolamins as green building materials of functional delivery vehicles to improve the health benefits of bioactive compounds have surged due to their attractive advantages (e.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2022
The mechanistic target of rapamycin (mTOR) is assembled into signaling complexes of mTORC1 or mTORC2, and plays key roles in cell metabolism, stress response, and nutrient and growth factor sensing. Accumulating evidence from human and animal model studies has demonstrated a pathogenic role of hyperactive mTORC1 in age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) is a primary injury site in AMD.
View Article and Find Full Text PDFThe potential impacts of active packaging on the volatile composition of fruits during preservations largely associated with consumers' acceptance, yet was barely investigated. In this work, a biopolymer-coated polyethylene active film was developed and its effects on qualities and volatile compositions of fruits with different respiration rates were comprehensively investigated. Underlying reasons for the effect of active packaging on volatile composition change of fruits were elucidated through revealing ternary relationship among the packaging-shaped bacterial community, modified atmosphere and volatiles.
View Article and Find Full Text PDFThe IL-36 family, including IL-36α, IL-36β, IL-36γ, and IL-36R antagonist, belong to the IL-1 superfamily. It was reported that IL-36 plays a role in immune diseases. However, it remains unclear how IL-36 regulates inflammation.
View Article and Find Full Text PDFInterleukin (IL)-33, a member in the IL-1 family, plays a central role in innate and adaptive immunity; however, how IL-33 mediates cytotoxic T-cell regulation and the downstream signals remain elusive. In this study, we found increased mouse IL-33 expression in CD8 T cells following cell activation via anti-CD3/CD28 stimulation in vitro or lymphocytic choriomeningitis virus (LCMV) infection in vivo. Our cell adoptive transfer experiment demonstrated that extracellular, but not nuclear, IL-33 contributed to the activation and proliferation of CD8 , but not CD4 T effector cells in LCMV infection.
View Article and Find Full Text PDFMetformin is not only the first-line medication for the treatment of type 2 diabetes, but it is also effective as an anti-inflammatory, anti-oxidative and anti-tumor agent. However, the effect of metformin during viral hepatitis remains elusive. Using an adenovirus (Ad)-induced viral hepatitis mouse model, we found that metformin treatment significantly attenuated liver injury, with reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and liver histological changes, presumably decreased effector T cell responses.
View Article and Find Full Text PDFHydrogen sulfide (HS) as the third gasotransmitter molecule serves various biological regulatory roles in health and disease. Acrylonitrile (AN) is a common occupational toxicant and environmental pollutant, causing brain and liver damage in mammals. The biotransformation of AN is dependent-upon reduced glutathione (GSH), cysteine and other sulfur-containing compounds.
View Article and Find Full Text PDFInflammation and oxidative stress accompany aging. This study investigated the interplay between oxidative stress and inflammation in the lacrimal gland. C57BL/6 mice were used at 2 to 3, 12, and 24 months of age.
View Article and Find Full Text PDFBackground: The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases.
View Article and Find Full Text PDFThe retinal pigment epithelium (RPE) is a particularly vulnerable tissue to age-dependent degeneration. Over the life span, the RPE develops an expanded endo-lysosomal compartment to maintain the high efficiency of phagocytosis and degradation of photoreceptor outer segments (POS) necessary for photoreceptor survival. As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity.
View Article and Find Full Text PDFHypoxia-inducible factor 1 (HIF-1) is a critical nuclear transcription factor for adaptation to hypoxia; its regulatable subunit, HIF-1α, is a cytoprotective regulatory factor. We examined the effects of methylmercury (MeHg) in rat adrenal pheochromocytoma (PC12) cells and the rat hepatocyte cell line BRL. MeHg treatment led to time- and concentration-dependent toxicity in both lines with statistically significant cytotoxic effects at 5 μM and 10 μM in PC12 and BRL, respectively, at 0.
View Article and Find Full Text PDFThe retinal pigment epithelium (RPE), the outermost layer of the retina, provides essential support to both the neural retina and choroid. Additionally, the RPE is highly active in modulating functions of immune cells such as microglia, which migrate to the subretinal compartment during aging and age-related degeneration. Recently, studies have highlighted the important roles of microRNA (miRNA) in the coordination of general tissue maintenance as well as in chronic inflammatory conditions.
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