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While Resolvin D1 (RvD1) shows promise in resolving inflammation in experimental autoimmune encephalomyelitis (EAE), its pro-resolving roles on dendritic cells (DCs) remain unknown, and the chemical instability of RvD1 poses significant challenges to its drug development. This study aims to investigate whether 4-(2'-methoxyphenyl)-1-[2'-[N-(2â³-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-MPPF), a novel chemically stable analogue of RvD1, can play a pro-resolving role in EAE, particularly on DCs, and if p-MPPF could serve as a potential substitute for RvD1. We showed that both RvD1 and p-MPPF mediated the resolution of inflammation in EAE, as evidenced by ameliorated EAE progression, attenuated pathological changes in the spinal cord, altered cytokine expression profile in serum, and reduced proportion of pro-inflammatory immune cells in the spleen. Utilizing DCs derived from both the spleen and bone marrow of EAE, our investigation showed that RvD1 and p-MPPF prevented DC maturation, decreased pro-inflammatory cytokine secretion, shifted DCs away from a pro-inflammatory phenotype, increased the phagocytosis capacity of DCs, and suppressed their ability to induce differentiation of CD4+ T cells into Th1 and Th17 subsets. For underlying intracellular mechanisms, we found that RvD1 and p-MPPF down-regulated the lactate dehydrogenase A signaling pathways. Comparisons between RvD1 and p-MPPF showed that they exerted overlapped pro-resolving effects to a large extent. This study demonstrates that both RvD1 and p-MPPF exert therapeutic effects on EAE by mediating inflammation resolution, which is closely associated with modulating DC immune function towards a tolerogenic phenotype. SPM mimetics may serve as a more promising therapeutic drug.
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Itaconate is an immunoregulatory metabolite produced by the mitochondrial enzyme immune-responsive gene 1 (IRG1) in inflammatory macrophages. We recently identified an important mechanism by which itaconate is released from inflammatory macrophages. However, it remains unknown whether extracellular itaconate is taken up by non-myeloid cells to exert immunoregulatory functions. Here, we used a custom-designed CRISPR screen to identify the dicarboxylate transporter solute carrier family 13 member 3 (SLC13A3) as an itaconate importer and to characterize the role of SLC13A3 in itaconate-improved hepatic antibacterial innate immunity. Functionally, liver-specific deletion of Slc13a3 impairs hepatic antibacterial innate immunity in vivo and in vitro. Mechanistically, itaconate uptake via SLC13A3 induces transcription factor EB (TFEB)-dependent lysosomal biogenesis and subsequently improves antibacterial innate immunity in mouse hepatocytes. These findings identify SLC13A3 as a key itaconate importer in mouse hepatocytes and will aid in the development of potent itaconate-based antibacterial therapeutics.
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Common wheat (Triticum aestivum L.) is the world's primary food crop, and ensuring its safe production is of utmost importance for global peace and human development. However, the continuous threat of fungal diseases, including Fusarium head scab, rusts, sharp eyespot, and powdery mildew (PM), poses a significant challenge to production. PM caused by Blumeria graminis f. sp. tritici (Bgt) causes substantial yield losses. Heshangmai (HSM), a wheat landrace originating from Sichuan Province, possesses high levels of resistance to PM. A comprehensive study using a large segregating population of a cross between HSM and Ningmaizi119 (NMZ119) revealed a single recessive allele conferring resistance. The gene, provisionally designated PmHSM, was located on the long arm of chromosome 4A (4AL). Molecular marker analysis, PM response array, and an allelism test indicated that PmHSM is a novel recessive resistance gene that shares an allelic relationship with PmHHXM. Thirteen simple sequence repeat (SSR) markers were developed using the sequence information of the 4AL region in the Chinese spring reference sequence v2.1 (CS RefSeq v2.1). PmHSM was flanked by markers Xmp1567 and Xmp1444 at genetic distances of 0.11 cM and 0.18 cM, respectively, and co-segregated with markers Xmp1439/Xmp1440/Xmp1442.
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Malondialdehyde (MDA) and formaldehyde (FA) are highly active carbonyl substances widely present in both biological and abiotic systems. The detection of MDA and FA is of great significance for disease diagnosis and food safety monitoring. However, due to the similarity in structural properties between MDA and FA, very few probes for synergistically detecting MDA and FA were reported. In addition, functional abnormalities in the Golgi apparatus are closely related to MDA and FA, but currently there are no fluorescent probes that can detect MDA and FA in the Golgi apparatus. Therefore, we constructed a simple Golgi-targetable fluorescent probe GHA based on hydrazine moiety as the recognition site to produce a pyrazole structure after reaction with MDA and to generate a CN double bond after reaction with FA, allowing MDA and FA to be distinguished due to different emission wavelengths during the recognition process. The probe GHA has good specificity and sensitivity. Under the excitation of 350 nm, the blue fluorescence was significantly enhanced at 424 nm when the probe reacted with MDA, and the detection limit was 71 nM. At the same time, under the same excitation of 350 nm, the reaction with FA showed a significant enhancement of green fluorescence at 520 nm, with a detection limit of 12 nM for FA. And the simultaneous and high-resolution imaging of MDA and FA in the Golgi apparatus of cells was achieved. In addition, the applications of the probe GHA in food demonstrated it can provide a powerful method for food safety monitoring. In summary, this study offers a promising tool for the synergistic identification and determination of MDA and FA in the biosystem and food, facilitating the revelation of their detailed functions in Golgi apparatus and the monitoring of food safety.
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Colorantes Fluorescentes , Formaldehído , Aparato de Golgi , Malondialdehído , Formaldehído/química , Formaldehído/análisis , Aparato de Golgi/química , Aparato de Golgi/metabolismo , Colorantes Fluorescentes/química , Humanos , Malondialdehído/análisis , Malondialdehído/química , Límite de Detección , Análisis de los Alimentos/métodos , Células HeLa , Imagen Óptica , Hidrazinas/química , Hidrazinas/análisis , Contaminación de Alimentos/análisisRESUMEN
Early treatment significantly improves the survival rate of liver cancer patients, so the development of early diagnostic methods for liver cancer is urgent. Liver cancer can develop from viral hepatitis, alcoholic liver, and fatty liver, thus making the above diseases share common features such as elevated viscosity, reactive oxygen species, and reactive nitrogen species. Therefore, accurate differentiation between other liver diseases and liver cancer is both a paramount practical need and challenging. Numerous fluorescent probes have been reported for the diagnosis of liver cancer by detecting a single biomarker, but these probes lack specificity for liver cancer in complex biological systems. Obviously, using multiple liver cancer biomarkers as the basis for judgment can dramatically improve diagnostic accuracy. Herein, we report the first fluorescent probe, LD-TCE, that sequentially detects carboxylesterase (CE) and lipid droplet polarity in liver cancer cells with high sensitivity and selectivity, with linear detection of CE in the range of 0-6 U/mL and a 65-fold fluorescence enhancement in response to polarity. The probe first reacts with CE and releases weak fluorescence, which is then dramatically enhanced due to the decrease in lipid droplet polarity in liver cancer cells. This approach allows the probe to enable specific imaging of liver cancer with higher contrast and accuracy. The probe successfully achieved the screening of liver cancer cells and the precise identification of liver cancer in mice. More importantly, it is not disturbed by liver fibrosis, which is a common pathological feature of many liver diseases. We believe that the LD-TCE is expected to be a powerful tool for early diagnosis of liver cancer.
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Carboxilesterasa , Colorantes Fluorescentes , Neoplasias Hepáticas , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Neoplasias Hepáticas/diagnóstico , Animales , Carboxilesterasa/metabolismo , Ratones , Imagen Óptica , Gotas Lipídicas/química , Gotas Lipídicas/metabolismo , Ratones Endogámicos BALB CRESUMEN
The highly reactive hypobromous acid (HOBr), which is generated after chlorination process of tap water, acts as a precursor of toxic brominated disinfection by-products (Br-DBPs) and further reacts with organic matter. In addition, HOBr produced from the oxidation of Br- during the degradation of pollutants by peroxymonosulfate (PMS, HSO5-) can be considered as the cause of the expedited degradation of pollutants. Therefore, it is particularly important to detect HOBr level in the water environment. Resazurin was selected as a fluorescent probe for selective recognition of HOBr in the water environment. The probe exhibited excellent spectral performance and showed high sensitivity to HOBr (LOD = 515 nM). This method has a relatively ideal recovery rate for HOBr detection in environmental water samples. Furthermore, the HOBr production during the chlorination disinfection process was simulated and the HOBr generated from this process was detected by the probe. Importantly, the process of HOBr recognition by the probe is accompanied by the change of color. Based on this, the relationship between the change of color B/G value and HOBr concentration was successfully constructed. The probe was loaded on the filter paper to make a test strip, which was utilized to the detection of HOBr. Collectively, this work provided a promising and powerful method for HOBr detection in the environment.
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Bromatos , Colorimetría , Colorantes Fluorescentes , Contaminantes Químicos del Agua , Colorantes Fluorescentes/química , Colorimetría/métodos , Bromatos/análisis , Bromatos/química , Contaminantes Químicos del Agua/análisis , Espectrometría de Fluorescencia/métodos , Límite de DetecciónRESUMEN
Iron is an essential element in the composition of living organisms and plays a crucial role in a wide range of biological activities. The human body primarily obtains essential iron through the consumption of food. Therefore, it is vital for the health of human body to maintain iron homeostasis. The reducing character of the cellular microenvironment enables Fe2+ to occupy a dominant position within the cell. Hence, there is an urgent need for a simple and sensitive tool that can detect a large amount of Fe2+ in organisms. In this work, a highly specific fluorescent chemodosimeter NPCO ("NP" represents the naphthalimide fluorophore, and "CO" represents the carbamoyl oxime structure) for the detection of Fe2+ with excellent sensitivity (LOD = 82 nM) was constructed by incorporating a novel carbamoyl oxime structure as the recognition group. NPCO can be effectively employed for the detection of Fe2+ in food samples, living cells, and zebrafish. Furthermore, by using soybean sprouts as a model plant, the application of NPCO was expanded to detect Fe2+ in plants. Therefore, NPCO could be used as an excellent assay tool for detecting Fe2+ in organisms and is expected to be an important aid in exploring the mechanism of iron regulation.
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Colorantes Fluorescentes , Hierro , Oximas , Pez Cebra , Colorantes Fluorescentes/química , Humanos , Animales , Hierro/análisis , Hierro/química , Oximas/químicaRESUMEN
Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased. Postoperative progression-free survival (PFS) rates between patients with positive and negative preoperative CTC results, and for CA19-9, CEA were significantly different. The positive rate of CTCs was 61% before chemotherapy and 23% after chemotherapy, and the correlation coefficient between the two was 0.385. Those whose CTC values increased after chemotherapy had shorter PFS rates. CTCs are an independent predictor of recurrence. Patients with CTC-positive results are more susceptible to recurrence. The CTC count in peripheral blood has a close bearing on the postoperative chemotherapy efficacy of patients with CRC and affects patients' PFS.
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Developing multifunctional films with antibacterial, antioxidant, and sustained-release properties is a robust strategy for preventing contamination of perishable fruits by foodborne microorganisms. This study engineered a sustained-release biodegradable antibacterial film loaded with EGCG (Pickering emulsion (PE)/α-Cyclodextrin (α-CD)/Konjac glucomannan (KGM)) through multi-strategy cross-linking for fruit preservation. EGCG is stabilized using PE and incorporated into the α-CD/KGM inclusion compound; the unique structure of α-CD enhances EGCG encapsulation, while KGM provides the film toughness and surface adhesion. The composite film's physicochemical properties, antioxidant, bacteriostatic and biodegradability were studied. Results showed that Pickering emulsions with 3 % oil phase exhibited excellent stability. Moreover, α-CD introduction increased the loading and sustained release of EGCG from the film, and its concentration significantly affected the light transmission, thermal stability, mechanical strength, mechanical characteristics and antioxidant capacity of the composite membrane. Antioxidant and antimicrobial activities of the composite film increased significantly with increasing α-CD concentration. Application of the film to tomatoes and strawberries effectively inhibited Escherichia coli and Staphylococcus aureus growth, prolonging the shelf-life of the fruits. Notably, the composite film exhibits superior biodegradability in soil. This EGCG-loaded PE/α-CD/KGM composite film is anticipated to be a multifunctional antimicrobial preservation material with sustained-release properties and biodegradable for perishable food applications.
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Antibacterianos , Antioxidantes , Catequina , Emulsiones , Escherichia coli , Frutas , Mananos , alfa-Ciclodextrinas , alfa-Ciclodextrinas/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Mananos/química , Mananos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Frutas/química , Emulsiones/química , Antioxidantes/química , Antioxidantes/farmacología , Escherichia coli/efectos de los fármacos , Conservación de Alimentos/métodos , Staphylococcus aureus/efectos de los fármacos , Embalaje de Alimentos/métodos , Pruebas de Sensibilidad Microbiana , Reactivos de Enlaces Cruzados/química , Liberación de FármacosRESUMEN
Nitrite (NO2-) has been widely recognized by the international community as an important substance affecting water quality safety and human health, and the detection of NO2- has always been a hot topic for researchers. Fluorescent probe method is an emerging and ideal way for detecting NO2-. Due to the high dependence of the reported reactive NO2- fluorescent probes on strong acidic systems, using the idea of photochemistry, a fluorescence analysis method for detecting NO2- was proposed in this work to change the necessity of strong acidic solutions in probe detection process. A 365 nm UV-LED lamp was used to irradiate NO2- in aqueous solution to convert it into hydroxyl radicals (HO·), and capture the photodegradation product of NO2- using coumarin-3-carboxylic acid as probe 3-CCA that can react with HO· to generate only one type of strong fluorescent substance. This probe has excellent photostability, selectivity, and anti-interference ability, and can realize the quantitative detection of NO2- (0-15 µM) in pure aqueous solution with pH of 7.4. In addition, its application in actual water samples is also satisfactory, with a recovery rate of (85.91 %-107.30 %). Importantly, we hope that this photolysis strategy can open up the novel thinking to develop suitable fluorescent probes for the analysis and detection of some hardly detected analytes.
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Hydrogen peroxide (H2O2), as one of reactive oxygen species (ROS) widely present in the human body, is involved in a variety of physiological activities. Many human diseases are associated with abnormal levels of H2O2 in the body. Mitochondria are the main organelles producing H2O2 in the human body, and monitoring the level of H2O2 in mitochondria can help to deepen the understanding of the detailed functions of H2O2 in physiological activities. However, due to the highly dynamic nature of the cells, real-time quantitative monitoring of H2O2 levels in mitochondria remains an ongoing challenge. Herein, a novel highly immobilized mitochondria-targeting fluorescent probe (QHCl) for detection of H2O2 was reasonably constructed based on quinolinium dye containing benzyl chloride moiety. Spectral experimental results demonstrated QHCl possessed outstanding selectivity toward H2O2 (λex/em = 380/513 nm). In addition, QHCl can quantitatively detect H2O2 in the concentration range of 0-20 µM with excellent sensitivity (LOD = 0.58 µM) under the PBS buffer solution (10 mM, pH = 7.4). Finally, bioimaging experiments demonstrated that the probe QHCl was able to be used for accurately detecting both endogenous and exogenous H2O2 in the mitochondria of living cells and zebrafish by its unique mitochondrial immobilization.
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Colorantes Fluorescentes , Peróxido de Hidrógeno , Mitocondrias , Pez Cebra , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/química , Colorantes Fluorescentes/química , Mitocondrias/metabolismo , Mitocondrias/química , Humanos , Animales , Células HeLa , Imagen ÓpticaRESUMEN
Myocardial ischemia/reperfusion injury (MIRI) is an irreversible adverse event during the management of coronary heart disease that lacks effective controls. The underlying mechanism of MIRI still requires further investigation. Recent studies have suggested that overexpression of ATF3 protects against MIRI by regulating inflammatory responses, ferroptosis, and autophagy. The downstream target of ATF3, EGR1, also showed cardioprotective properties against MIRI by promoting autophagy. Therefore, further investigating the effect of ATF3/EGR1 pathway on MIRI-induced inflammation and autophagy is needed. Cardiomyocyte MIRI model was established by challenging H9C2 cells with hypoxia/reoxygenation (H/R). The ATF3 overexpression-H/R cell model by transfecting ATF3 plasmid into the H9C2 cell line. The transcription levels of ATF3 and EGR1 were determined using RT-qPCR, the levels of TNF-α and IL-6 were determined using ELISA kits, the protein expression of LC3 I, LC3 II, and P62 was determined via WB, and microstructure of H9C2 cell was observed by transmission electron microscopy (TEM). Overexpression of ATF3 significantly downregulated Egr1 levels, indicating that EGR1 might be the target of ATF3. By upregulating ATF3 levels, the extracellular levels of the inflammatory cytokines TNF-α and IL-6 significantly decreased, and the protein expression of the autophagy markers LC3 I, LC3 II, and P62 significantly increased. TEM results revealed that the cell line in the H/R-ATF3 group exhibited a higher abundance of autophagosome enclosures of mitochondria. The results indicated that ATF3/EGR1 may alleviate inflammation and improve autophagy in an H/R-induced MIRI model of cardiomyocytes.
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Factor de Transcripción Activador 3 , Autofagia , Proteína 1 de la Respuesta de Crecimiento Precoz , Inflamación , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Factor de Necrosis Tumoral alfa , Factor de Transcripción Activador 3/metabolismo , Factor de Transcripción Activador 3/genética , Autofagia/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Animales , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , Ratas , Línea Celular , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Transducción de Señal , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/genéticaRESUMEN
Boron carbonitride (BCN) films containing hybridized bonds involving B, C, and N over wide compositional ranges enable an abundant variety of new materials, properties, and applications; however, their electronic performance is still limited by the presence of structural and electronic defects, yielding sluggish mobility and electrical conductivity. This work reports on mechanically stable BCN films and their corresponding optical and electronic properties. The ternary BCN films consisting of hybridized B-C-N bonds have been achieved by varying N2 flow by the radio frequency magnetron sputtering method. The BCN films show a bandgap value ranging from 3.32 to 3.82 eV. Hall effect measurements reveal an n-type conductivity with an improved hall mobility of 226 cm2/V s at room temperature for the optimal film. The n-BCN/p-Si heterojunctions exhibit a nonlinear rectifying characteristic, where the tunneling behavior dominates the injection regimes due to the density of defects, i.e., structural disorder and impurities. Our work demonstrates the tunable electrical properties of BCN/Si p-n diodes and, thus, is beneficial for the potential application in the fields of optics, optoelectronics, and electrics.
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Plant pathogenic fungi elaborate numerous detoxification strategies to suppress host reactive oxygen species (ROS), but their coordination is not well-understood. Here, we show that Sirt5-mediated protein desuccinylation in Magnaporthe oryzae is central to host ROS detoxification. SIRT5 encodes a desuccinylase important for virulence via adaptation to host oxidative stress. Quantitative proteomics analysis identified a large number of succinylated proteins targeted by Sirt5, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, and fatty acid oxidation. Deletion of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH : NADP+ and GSH : GSSG ratios, disrupting redox balance and impeding invasive growth. Sirt5 desuccinylated thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding. Altogether, this work demonstrates the importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during M. oryzae infection.
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Ascomicetos , Magnaporthe , Oryza , Especies Reactivas de Oxígeno/metabolismo , Lisina/metabolismo , Estrés Oxidativo , Ascomicetos/metabolismo , Proteínas Fúngicas/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/microbiologíaRESUMEN
OBJECTIVES: The current methods for detecting myelin changes in ischemic stroke are indirect and cannot accurately reflect their status. This study aimed to develop a novel fluorescent-magnetic resonance dual-modal molecular imaging probe for direct imaging of myelin. METHODS: Compounds 7a and 7b were synthesized by linking the MeDAS group and Gadolinium (III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate. Compound 7a was selected for characterization and further study. Cell uptake, cytotoxicity, and magnetic resonance imaging scans were performed on cells. In vitro experiments on frozen brain sections from 7-day-old, 8-week-old, and ischemic stroke rats were compared with commercially available Luxol Fast Blue staining. After HPLC and MR scanning, brain tissue was soaked in 7a and scanned using T1WI and T1maps sequences. RESULTS: Spectrophotometer results showed that compounds 7a and 7b had fluorescent properties. MR scans indicated that the compounds had contrast agent properties. Cells could uptake 7a and exhibited high signals in imaging scans. Compound 7a brain tissue staining showed more fluorescence in myelin-rich regions and identified injury sites in ischemic stroke rats. MR scanning of brain sections provided clear myelin contrast. CONCLUSION: A novel fluorescent-magnetic resonance dual-modal molecular imaging probe for direct imaging of myelin was successfully developed and tested in rats with ischemic stroke. These findings provide new insights for the clinical diagnosis of demyelinating diseases.
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Accidente Cerebrovascular Isquémico , Imagen por Resonancia Magnética , Ratas , Animales , Fluorescencia , Imagen por Resonancia Magnética/métodos , Isquemia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Accidente Cerebrovascular Isquémico/patología , Medios de ContrasteRESUMEN
OBJECTIVE: To explore the expression and functional role of Krüpple-like factor 4 (KLF4) protein stimulated by tumor necrosis factor α (TNF-α) in SK-BR-3 breast cancer cells. METHODS: SK-BR-3 cells were stimulated with various concentrations of TNF-α at 0, 1, 5, 10, and 20 ng/mL. Expression levels of KLF4 protein were detected by Western blotting. In the detection of apoptosis, flow cytometry, and DAPI staining were used for detecting the level of apoptosis. RESULTS: KLF4 expression was markedly elevated following stimulation of SK-BR-3 with TNF-α. At the same time, the expression of KLF4 protein increased gradually with the increase of TNF-α stimulation concentration. TNF-α stimulation of SK-BR-3 cells increased apoptosis as measured by apoptosis levels. By overexpressing KLF4 protein in SK-BR-3 cells, it similarly increased apoptosis and promoted cell death of SK-BR-3 cells. CONCLUSION: TNF-α promotes KLF4 expression, while TNF-α promotes apoptosis in SK-BR-3 cells, a process that may be due to elevated KLF4 protein expression.
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Itaconate is a metabolite that synthesized from cis-aconitate in mitochondria and transported into the cytosol to exert multiple regulatory effects in macrophages. However, the mechanism by which itaconate exits from macrophages remains unknown. Using a genetic screen, we reveal that itaconate is exported from cytosol to extracellular space by ATP-binding cassette transporter G2 (ABCG2) in an ATPase-dependent manner in human and mouse macrophages. Elevation of transcription factor TFEB-dependent lysosomal biogenesis and antibacterial innate immunity are observed in inflammatory macrophages with deficiency of ABCG2-mediated itaconate export. Furthermore, deficiency of ABCG2-mediated itaconate export in macrophages promotes antibacterial innate immune defense in a mouse model of S. typhimurium infection. Thus, our findings identify ABCG2-mediated itaconate export as a key regulatory mechanism that limits TFEB-dependent lysosomal biogenesis and antibacterial innate immunity in inflammatory macrophages, implying the potential therapeutic utility of blocking itaconate export in treating human bacterial infections.
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Inmunidad Innata , Succinatos , Animales , Humanos , Ratones , Antibacterianos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Lisosomas/metabolismo , Proteínas de Neoplasias/metabolismo , Succinatos/farmacología , Succinatos/metabolismoRESUMEN
Carbon monoxide (CO) not only causes damage to life and health as an environmental pollutant, but also undertakes many physiological functions in organisms. In particular, developing means that can be used for the determination of CO in organelles will provide insight into the vital role it plays. Studies have shown that mitochondrial respiration is closely related to CO concentrations, so it is critical to develop tools for CO detection in mitochondria. Here, we use a rhodamine derivative that can target mitochondria as fluorophores to construct a mitochondrial-labeled CO fluorescence probe (Rh-CO) with high sensitivity (detection limit: 9.4 nM), excellent water-solubility, and long emission (λem = 630 nm). Prominently, the probe has outstanding mitochondria-targeting capabilities. Moreover, we used transient glucose deprivation (TGD) and heme to stimulate endogenous CO production in living cells and zebrafish, respectively, and the probe exhibited excellent imaging capabilities. All in all, we expect this probe to contribute to a deeper understanding of the role played by CO in mitochondria.
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Colorantes Fluorescentes , Pez Cebra , Animales , Humanos , Imagen Óptica , Células HeLa , MitocondriasRESUMEN
AIMS: Experimental autoimmune encephalomyelitis (EAE) is a widely used mouse model of multiple sclerosis. Rather than inducing immune response, tolerogenic dendritic cells (tDCs) have the ability to induce immune tolerance. In previous studies, we induced tDCs by 1,25-(OH)2D3 and 1,25-(OH)2D3 DCs significantly alleviated EAE symptoms. As downstream targets of 1,25-(OH)2D3, inhibition of RelB and MyD88 expression in DCs might induce tDCs and has therapeutic effect of MS. METHODS: Knockdown the expression of RelB and MyD88 with shRNA lentivirus to induce tDCs, adoptive transfer these tDCs to EAE mice, and investigate their therapeutic effects. RESULTS: Reduction of RelB expression induced tDCs. After transferring into EAE mice, tDCs with low RelB expression significantly alleviate their symptoms as well as reduce the immune cell infiltration and demyelination in spinal cord. CONCLUSION: RelB plays a key role in the antigen presenting function of DCs, and tDCs with low RelB expression is a potential treatment for EAE and MS.
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Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Animales , Ratones , Células Dendríticas , Esclerosis Múltiple/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Médula Espinal/metabolismoRESUMEN
Cancer is "the sword of Damocles" that threatens human life and health. Therefore, the diagnosis and treatment of cancer have been receiving much attention. Many overexpressed receptors on the surface of cancer cells provide us with an effective way to specifically identify the cancer cells, and receptor targeting strategies are becoming one of the hot ideas to enhance the ability of fluorescent probes to target tumors. Fluorescent probes connected to ligands are targeted at cancer cell surfaces through receptor-mediated endocytosis. Receptor-targeting probes can image and track cancer cells, determine tumor boundaries, monitor deep lesions, and play a role in clinical medicine, such as fluorescent imaging-guided surgery. In this review, based on the perspective of small molecule fluorescent probes, we reviewed the design ideas, photophysical properties, and applications of receptor-targeting probes for detecting biomarkers in imaging and tracing cancer cells and prospected the future developmental direction of such probes. We hope that this review will provide more ideas for the design and development of active targeting probes for receptors and lead to more applications in the medical field.