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Serum amyloid A (SAA) are major acute-phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin-induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU-induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro-inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro-inflammatory factors, and increased the expression of tissue-reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll-like receptor 4 (TLR4). Collectively, our study suggested that microglial cell-expressed SAA could be a potential target in treating acute ocular inflammation.
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Microglia , Proteína Amiloide A Sérica , Animais , Camundongos , Proteína Amiloide A Sérica/genética , Inflamação/induzido quimicamente , Retina , Proteínas de Fase Aguda , Endotoxinas/toxicidadeRESUMO
Aging is a major risk factor for the development or the worsening of retinal degenerative conditions. The intricate network of the neural retina determined that the retinal aging is a complicated process. The aim of this study is to delineate the transcriptomic changes of major retinal neurons during aging in C57BL/6 mice at single-cell level. We analyzed the transcriptional profiles of the photoreceptor, bipolar, amacrine, and Müller glial cells of 1.5-2 and 24-30 months old mice using single-cell RNA sequencing technique. We selectively confirmed the differences in gene expression using immunofluorescence staining and RNA in situ hybridization analysis. We found that each retinal cell type had unique changes upon aging. However, they all showed signs of dysregulated glucose and energy metabolism, and perturbed proteostasis. In particular, old Müller glia exhibited the most profound changes, including the upregulation of cell metabolism, stress-responses, antigen-presentation and immune responses and metal ion homeostasis. The dysregulated gliogenesis and differentiation was confirmed by the presence of Müller glia expressing rod-specific genes in the inner nuclear layer and the outer plexiform layer of the old retina. We further pinpointed the specific loss of GABAergic amacrine cells in old retina. Our study emphasized changes of amacrine and Müller glia during retinal aging, provided resources for further research on the molecular and cellular regulatory mechanisms underlying aging-associated retinal deterioration.
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Envelhecimento , Células Amácrinas , Metabolismo Energético , Camundongos Endogâmicos C57BL , Proteostase , Animais , Células Amácrinas/metabolismo , Camundongos , Envelhecimento/fisiologia , Metabolismo Energético/fisiologia , Células Ependimogliais/metabolismo , Retina/metabolismo , Neurônios GABAérgicos/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/genética , Hibridização In Situ , Homeostase/fisiologiaRESUMO
This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy.
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Neoplasias Hepáticas , Nanopartículas , Humanos , Silício , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , GalactosaminaRESUMO
BACKGROUND: Chitosan oligosaccharides, with an average molecular weight ≤ 1000 Da (COST), is a natural marine product that has the potential to improve intestinal microflora and resist lipid metabolism disorders. METHODS: First, by establishing a mice model of lipid metabolism disorder induced by a high fat and high sugar diet, it is proven that COST can reduce lipid metabolism disorder, which may play a role in regulating intestinal microorganisms. Then, the key role of COST in the treatment of intestinal microorganisms is further confirmed through the method of COST-treated feces and fecal bacteria transplantation. CONCLUSIONS: intestinal microbiota plays a key role in COST inhibition of lipid metabolism disorder induced by a high fat and high sugar diet. In particular, COST may play a central regulatory role in microbiota, including Bacteroides, Akkermansia, and Desulfovibrio. Taken together, our work suggests that COST may improve the composition of gut microbes, increase the abundance of beneficial bacteria, improve lipid metabolism disorders, and inhibit the development of metabolic disorders.
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Microbioma Gastrointestinal , Transtornos do Metabolismo dos Lipídeos , Animais , Bactérias , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , AçúcaresRESUMO
Chitosan obtained from abundant marine resources has been proven to have a variety of biological activities. However, due to its poor water solubility, chitosan application is limited, and the degradation products of chitosan oligosaccharides are better than chitosan regarding performance. Chitosan oligosaccharides have two kinds of active groups, amino and hydroxyl groups, which can form a variety of derivatives, and the properties of these derivatives can be further improved. In this review, the key structures of chitosan oligosaccharides and recent studies on chitosan oligosaccharide derivatives, including their synthesis methods, are described. Finally, the antimicrobial and antitumor applications of chitosan oligosaccharides and their derivatives are discussed.
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Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Organismos Aquáticos , Quitosana/farmacologia , Oligossacarídeos/farmacologia , Animais , Antibacterianos/química , Antineoplásicos/química , Quitosana/química , Oligossacarídeos/química , Relação Estrutura-AtividadeRESUMO
In this study, C57BL/6 mice were given an HFHSD diet for 8 weeks to induce hepatic steatosis and then given COSM solution orally for 12 weeks. The study found that the HFHSD diet resulted in steatosis and insulin resistance in mice. The formation of NAFLD induced by HFHSD diet was related to the imbalance of intestinal flora. However, after COSM intervention, the abundance of beneficial bacteria increased significantly, while the abundance of harmful bacteria decreased significantly. The HFHSD diet also induced changes in intestinal bacterial metabolites, and the content of short-chain fatty acids in cecal contents after COSM intervention was significantly higher than that in the model group. In addition, COSM not only improved LPS levels and barrier dysfunction in the ileum and colon but upregulated protein levels of ZO-1, occludin, and claudin in the colon and downregulated the liver LPS/TLR4/NF-κB inflammatory pathway. We concluded that the treatment of marine chitooligosaccharide COSM could improve the intestinal microflora structure of the fatty liver and activate an inflammatory signaling pathway, thus alleviating the intrahepatic lipid accumulation induced by HFHSD.
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Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Quitosana , Dieta Hiperlipídica , Lipopolissacarídeos/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , OligossacarídeosRESUMO
Marine crustacean waste has not been fully utilized and is a rich source of chitin. Enzymatic degradation has attracted the wide attention of researchers due to its unique biocatalytic ability to protect the environment. Chitosan (CTS) and its derivative chitosan oligosaccharides (COSs) with various biological activities can be obtained by the enzymatic degradation of chitin. Many studies have shown that chitosan and its derivatives, chitosan oligosaccharides (COSs), have beneficial properties, including lipid-lowering, anti-inflammatory and antitumor activities, and have important application value in the medical treatment field, the food industry and agriculture. In this review, we describe the classification, biochemical characteristics and catalytic mechanisms of the major degrading enzymes: chitinases, chitin deacetylases (CDAs) and chitosanases. We also introduced the technology for enzymatic design and modification and proposed the current problems and development trends of enzymatic degradation of chitin polysaccharides. The discussion on the characteristics and catalytic mechanism of chitosan-degrading enzymes will help to develop new types of hydrolases by various biotechnology methods and promote their application in chitosan.
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Quitinases , Quitosana , Animais , Quitina/química , Quitinases/metabolismo , Quitosana/química , Crustáceos/metabolismo , Oligossacarídeos/químicaRESUMO
The sensitive chitosan (CTS) detection methods based on the resonance Rayleigh scattering (RRS) quenching method and fluorescence quenching of Eosin Y were put forward. In the HAC-NaAC buffer solution, Eosin Y interacted with Triton X-100 to generate the binary complex which served as the RRS spectral probe. When CTS was interacted with the binary complex, the RRS intensity decreased with the increase of CTS. At the same time, the fluorescence intensity of Eosin Y decreased in the presence of Triton X-100, and the fluorescence intensity of "Eosin Y+Triton X-100" system further decreased when CTS was added. So it was further proved that there was a forming complex in "Eosin Y+Triton X100+CTS" system. The interaction was characterized by zeta potential, RRS, fluorescence spectrum, and UV-Vis spectroscopy. Under optimal conditions, there was a good linear relationship between the RRS decreased intensity (ΔI) and the concentration of CTS in the range of 0.05-1.30 µg/mL, with a regression equation of ΔI = 1325c + 73.66 and correlation coefficient (R2) of 0.9907. The detection limit was 0.0777 µg/mL. Likewise, the linear range of the fluorescence quenching was 0.03-1.30 µg/mL; the regression equation was ΔF = 1926c + 294.0 with R2 = 0.9800 under fluorescence quenching. The detection limit was 0.0601 µg/mL. Therefore, the dual-channel sensor for the determination of CTS was applied to the health products, and the results were satisfactory. The t test result showed that there was no statistical difference between the two methods.
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Quitosana/análise , Amarelo de Eosina-(YS)/química , Corantes Fluorescentes/química , Cápsulas , Limite de Detecção , Espectrometria de Fluorescência/métodosRESUMO
A rapid method for colorimetric monitoring of bacterial viability is described. The colorimetric method was carried out based on glucose oxidase-encapsulated Zn/Co-infinite coordination polymer (Zn/Co-ICP@GOx), which was prepared in aqueous solution free of toxic organic solvents at room temperature. The Zn/Co-ICP@GOx was confirmed to be a robust sphere structure with an average diameter of 147.53 ± 20.40 nm. It integrated the catalytic activity of natural enzyme (GOx) and mimetic peroxidase (Co (Ð)) all in one, efficiently acting as a biocatalytic cascade platform for glucose catalytic reaction. Exhibiting good multi-enzyme catalytic activity, stability, and selectivity, Zn/Co-ICP@GOx can be used for colorimetric glucose detection. The linear range was 0.01-1.0 mmol/L, and the limit of detection (LOD) was 0.005 mmol/L. As the glucose metabolism is a common expression of bacteria, the remaining glucose can indirectly represent the bacterial viability. Hence, a Zn/Co-ICP@GOx-based colorimetric method was developed for monitoring of bacterial viability. The color was intuitively observed with the naked eye, and the bacterial viability was accurately quantified by measurement of the absorbance at 510 nm. The method was applied to determination of bacterial viability in water and milk samples with recoveries of 99.0-103% and RSD of 0.43-7.5%. The method was rapid (less than 40 min) and applicable to different bacterial species irrespective of Gram-positive and Gram-negative bacteria, providing a universal and promising strategy for real-time monitoring of bacterial viability.
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Bactérias/metabolismo , Colorimetria/métodos , Complexos de Coordenação/química , Glucose/análise , Viabilidade Microbiana , Nanosferas/química , Animais , Biocatálise , Técnicas Biossensoriais/métodos , Cobalto/química , Enzimas Imobilizadas/química , Glucose/química , Glucose Oxidase/química , Leite/microbiologia , Microbiologia da Água , Zinco/químicaRESUMO
It remains a problem for direct detection of small inorganic nitrite ions using resonance Rayleigh scattering (RRS) method based on the direct dye-binding reaction. In the present study, a redox-derivatization reaction taking only 5 min was introduced prior to nitrite detection. In the redox-derivatization reaction, nitrite ions were reduced by excess iodine ions to generate triiodide ions (I3-), which were further derivatized with a cationic dye (basic violet 1, BV1) to form the ion associates of I3--BV1. Therefore, the RRS signal was significantly enhanced, resulting from the increase of particle size and resonance-enhanced scattering effect. The analytical procedure was performed by just mixing nitrite, oxidant, acid, and dye all-in-one, avoiding the tediousness of a multi-step process or the preparation of nanoparticles. The whole detection process including the redox-derivatization reaction was less than 6 min. The reaction conditions such as concentration of hydrochloric acid, potassium iodide, and BV1, reaction time, and temperature were investigated. Under optimum conditions, the concentration of nitrite was linear with an RRS signal of I3--BV1 ion associates at 320 nm in the range of 0.015-1.2 mg/L. The limit of detection (LOD) was calculated to be 3.0 µg/L. The RRS method was applied to the determination of nitrite in real samples such as pork sausage, milk powder, and water with recovery of 95.2-112%. With advantages of rapidness, high sensitivity, and high selectivity, the method indicates potential applicability for detection of nitrite in complex samples. The method also provides an instructive protocol for detection of analytes that generate no/weak RRS enhancement after the direct dye-binding reaction. Graphical abstract.
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This work described the use of a basic phenothiazine dye (toluidine blue, TB) as a resonance Rayleigh scattering (RRS) and colorimetric probe for the detection of perfluorooctane sulfonate (PFOS). Owing to the electrostatic interactions between TB and PFOS, TB in the presence of PFOS caused great enhancement of RRS signal at dual-wavelength (I345 nm and I506 nm) and the ratio changes of absorbance (A502 nm/A630 nm). The RRS enhancement was attributed to the absorption-rescattering resonance effect, the increase of the molecular size, and the enhancement of hydrophobicity. The analytical procedure was implemented by physically mixing TB, Britton-Robinson buffer solution, and PFOS solution (or sample solution) all-in-one, avoiding the tedious pre-derivatization or the preparation of nanoparticles. The whole approach was less than 8 min. Under the optimal conditions, the analytical performance was acquired. The linear ranges for RRS and colorimetry were 0.04-8.0 and 1.0-20 µmol/L, with detection limits of 4.2 nmol/L and 112 nmol/L, respectively. The RRS method was applied to the determination of PFOS in environmental water with recoveries of 93.2-106%. The dual-channel sensor is convenient, rapidly responsive, sensitive, and cost-effective, integrating the advantages of RRS and colorimetry. Graphical abstract.
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Sensitive and selective detection of harmful gas is an important task in environmental monitoring. In this work, a gas sensor based on cataluminescence (CTL) for detection of acetaldehyde was designed by using nano-NiO as the sensing material. The sensor shows sensitive response to acetaldehyde at a relatively low working temperature of 200 °C. The linear range of CTL intensity versus acetaldehyde concentration is 0.02-2.5 mg/L, with a limit of detection of 0.006 mg/L at a signal-to-noise ratio of three. Mechanism study shows that electronically excited CO2 is the excited intermediate for CTL emission during the catalytic oxidation of acetaldehyde on the NiO surface. The proposed sensor has promising application in monitoring acetaldehyde in residential buildings and in the workplace.
Assuntos
Acetaldeído/análise , Medições Luminescentes , Nanopartículas/química , Níquel/química , CatáliseRESUMO
BACKGROUND: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.
Assuntos
Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de SobrevidaRESUMO
Poor selectivity and biocompability remain problems in applying surface-enhanced Raman spectroscopy (SERS) for direct detection of proteins due to similar spectra of most proteins and overlapping Raman bands in complex mixtures. To solve these problems, an aptamer recognition induced target-bridged strategy based on magnetic chitosan (MCS) and silver/chitosan nanoparticles (Ag@CS NPs) using SERS was developed for detection of protein benefiting from specific affinity of aptamers and biocompatibility of chitosan (CS). In this process, one aptamer (or antibody) modified MCS worked as capture probes through the affinity binding site of protein. The other aptamer modified Raman report molecules encapsulated Ag@CS NPs were used as SERS sensing probes based on the other binding site of protein. The sandwich complexes of aptamer (antibody)/protein/aptamer were separated easily with a magnet from biological samples, and the concentration of protein was indirectly reflected by the intensity variation of SERS signal of Raman report molecules. To explore the universality of the strategy, three different kinds of proteins including thrombin, platelet derived growth factor BB (PDGF BB) and immunoglobulin E (lgE) were investigated. The major advantages of this aptamer recognition induced target-bridged strategy are convenient operation with a magnet, stable signal expressing resulting from preventing loss of report molecules with the help of CS shell, and the avoidance of slow diffusion-limited kinetics problems occurring on a solid substrate. To demonstrate the feasibility of the proposed strategy, the method was applied to detection of PDGF BB in clinical samples. The limit of detection (LOD) of PDGF BB was estimated to be 3.2 pg/mL. The results obtained from human serum of healthy persons and cancer patients using the proposed strategy showed good agreement with that of the ELISA method but with wider linear range, more convenient operation, and lower cost. The proposed strategy holds great potential in highly sensitive and selective analysis of target proteins in complex biological samples.
Assuntos
Aptâmeros de Peptídeos/química , Quitosana/química , Magnetismo , Nanopartículas , Proteínas/análise , Prata/química , Análise Espectral Raman/métodos , Limite de Detecção , Microscopia Eletrônica de Transmissão , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To explore associated proteins involved in age-related changes of the testis and better understand the roles of these proteins in the human testis. STUDY DESIGN: We used two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spec trometry analysis to identify differentially expressed proteins between the aged and the normal control groups. The L-lactate dehydrogenase C chain (LDHC) protein, a previous testis-specific protein, was found to be downregulated in the aged testis and was further tested with western blot and immunohistochemical analysis to verify the result of the LDHC protein in 2-DE. RESULTS: Twelve differentially expressed proteins were identified. Among those proteins, 3 were upregulated and 9 were downregulated in the aged group. The results of western blot and immunohistochemical analysis confirmed the expression of LDHC downregulation in the aged testis. Some proteins identified had little well-known function in the human testis, as follows: AKR7A3, FDXR, PGAM1, SEPT2 and HMGCS2. CONCLUSION: Our results imply that the aged testis can be a good model to find associated proteins involved in age-related changes of the testis. It can be useful to understand the roles of those proteins in the testis.
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Envelhecimento/fisiologia , Proteínas/análise , Proteômica , Testículo/química , Testículo/fisiologia , Idoso , Regulação para Baixo , Eletroforese em Gel Bidimensional , Humanos , Imuno-Histoquímica , Isoenzimas/análise , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Testículo/anatomia & histologia , Adulto JovemRESUMO
This paper proposed a rapid, selective and sensitive molybdenum yellow derivatization coupled with Resonance Rayleigh scattering (MYD-RRS) method for detection of phosphate. Under the acidic condition, phosphate can be selectively transformed to Keggin type of phosphomolybdic acid (PMA, i.e., PMo12O403-) through molybdenum yellow derivatization reaction prior to RRS detection. The PMA can further react with cationic methyl violet (MV) to form larger PMA-MV ion association complexes, generating significant RRS signal. The concentration of phosphate was linearly related to the RRS signal in the range of 8-200 ng/mL, with the determining coefficient (R2) of 0.9973 and the detection limit of 4 ng/mL. The analytical procedure can be completed within 10 min and the RRS signal intensity can remain stable more than 4 h. The method showed good stability toward temperature and time, and good anti-interference capability. The method was applied to the determination of phosphate in real food samples with the recovery of 85-117% and RSD of 1-5.2%. With the advantages of rapidness, high sensitivity and good selectivity, the MYD-RRS method exhibits great potential to the determination of phosphate in food. It also provides an instructive strategy for detection of analytes with weak RRS signal.
Assuntos
Molibdênio , Fosfatos , Espalhamento de RadiaçãoRESUMO
Retinal degeneration is a collection of devastating conditions with progressive loss of vision which often lead to blindness. Research on retinal microglial cells offers great therapeutic potential in deterring the progression of degeneration. This study explored the mechanisms underlying the TREM2-mediated protective function of activated microglial cells during retinal degeneration. N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was established in C57BL/6 J (WT) and Trem2 knockout (Trem2-/-) mice. We discovered that MNU treatment led to the concurrent processes of photoreceptor apoptosis and microglia infiltration. A significant upregulation of disease-associated microglia signature genes was observed during photoreceptor degeneration. Following MNU treatment, Trem2-/- mice showed exacerbated photoreceptor cell death, decreased microglia migration and phagocytosis, reduced microglial PPARγ activation and CD36 expression. Pharmaceutical activation of PPARγ promoted microglial migration, ameliorated photoreceptor degeneration and restored CD36 expression in MNU-treated Trem2-/- mice. Inhibition of CD36 activity worsened photoreceptor degeneration in MNU-treated WT mice. Our findings suggested that the protective effect of microglia during retinal degeneration was dependent on Trem2 expression and carried out via the activation of PPARγ and the consequent upregulation of CD36 expression. Our study linked TREM2 signaling with PPARγ activation, and provided a potential therapeutic target for the management of retinal degeneration.
Assuntos
Antígenos CD36 , Glicoproteínas de Membrana , Microglia , PPAR gama , Receptores Imunológicos , Degeneração Retiniana , Animais , Camundongos , Apoptose/efeitos dos fármacos , Antígenos CD36/metabolismo , Antígenos CD36/genética , Movimento Celular , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Metilnitrosoureia/toxicidade , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Microglia/patologia , Fagocitose , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras/patologia , PPAR gama/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Degeneração Retiniana/patologia , Degeneração Retiniana/metabolismoRESUMO
Oxidative stress is one of the important factors in the development of alcoholic liver disease. The production of reactive oxygen species and other free radicals is an important feature of alcohol metabolism in the liver and an important substance in liver injury. When large amounts of ROS are produced, the homeostasis of the liver REDOX system will be disrupted and liver injury will be caused. Oxidative stress can damage proteins, nucleic acids and lipids, liver dysfunction. In addition, damaging factors produced by oxidative damage to liver tissue can induce the occurrence of inflammation, thereby aggravating the development of ALD. This article reviews the oxidative damage of alcohol on liver proteins, nucleic acids, and lipids, and provides new insights and summaries of the oxidative stress process. We also discussed the relationship between oxidative stress and inflammation in alcoholic liver disease from different perspectives. Finally, the research status of antioxidant therapy in alcoholic liver disease was summarized, hoping to provide better help for learning and developing the understanding of alcoholic liver disease.
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The impact of plastic pollution on living organisms have gained significant research attention. However, the effects of nanoplastics (NPs) on retina remain unclear. This study aimed to investigate the effect of long-term polystyrene nanoparticles (PS-NPs) exposure on mouse retina. Eight weeks old C57BL/6 J mice were exposed to PS-NPs at the diameter of 100 nm and concentration of 10 mg/L in drinking water for 3 months. PS-NPs were able to penetrate the blood-retina barrier, accumulated at retinal tissue, caused increased oxidative stress level and reduced scotopic electroretinal responses without remarkable structural damage. PS-NPs exposure caused cytotoxicity and reactive oxygen species accumulation in cultured photoreceptor cell. PS-NPs exposure increased oxidative stress level in retinal pigment epithelial (RPE) cells, leading to changes of gene and protein expression indicative of compromised phagocytic activity and cell junction formation. Long-term PS-NPs exposure also aggravated light-induced photoreceptor cell degeneration and retinal inflammation. The transcriptomic profile of PS-NPs-exposed, light-challenged retinal tissue shared similar features with those of age-related macular degeneration (AMD) patients in the activation of complement-mediated phagocytic and proinflammatory responses. Collectively, these findings demonstrated the oxidative stress- and inflammation-mediated detrimental effect of PS-NPs on retinal function, suggested that long-term PS-NPs exposure could be an environmental risk factor contributing to retinal degeneration.
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Luz , Camundongos Endogâmicos C57BL , Nanopartículas , Estresse Oxidativo , Poliestirenos , Retina , Degeneração Retiniana , Epitélio Pigmentado da Retina , Animais , Poliestirenos/toxicidade , Poliestirenos/química , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Retina/efeitos dos fármacos , Retina/efeitos da radiação , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Eletrorretinografia , MasculinoRESUMO
G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.