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Journal of Immunology (Baltimore, Md. :... Aug 2023Activated T cells undergo metabolic reprogramming to meet anabolic, differentiation, and functional demands. Glutamine supports many processes in activated T cells, and...
Activated T cells undergo metabolic reprogramming to meet anabolic, differentiation, and functional demands. Glutamine supports many processes in activated T cells, and inhibition of glutamine metabolism alters T cell function in autoimmune disease and cancer. Multiple glutamine-targeting molecules are under investigation, yet the precise mechanisms of glutamine-dependent CD8 T cell differentiation remain unclear. We show that distinct strategies of glutamine inhibition by glutaminase-specific inhibition with small molecule CB-839, pan-glutamine inhibition with 6-diazo-5-oxo-l-norleucine (DON), or by glutamine-depleted conditions (No Q) produce distinct metabolic differentiation trajectories in murine CD8 T cells. T cell activation with CB-839 treatment had a milder effect than did DON or No Q treatment. A key difference was that CB-839-treated cells compensated with increased glycolytic metabolism, whereas DON and No Q-treated cells increased oxidative metabolism. However, all glutamine treatment strategies elevated CD8 T cell dependence on glucose metabolism, and No Q treatment caused adaptation toward reduced glutamine dependence. DON treatment reduced histone modifications and numbers of persisting cells in adoptive transfer studies, but those T cells that remained could expand normally upon secondary Ag encounter. In contrast, No Q-treated cells persisted well yet demonstrated decreased secondary expansion. Consistent with reduced persistence, CD8 T cells activated in the presence of DON had reduced ability to control tumor growth and reduced tumor infiltration in adoptive cell therapy. Overall, each approach to inhibit glutamine metabolism confers distinct effects on CD8 T cells and highlights that targeting the same pathway in different ways can elicit opposing metabolic and functional outcomes.
Topics: Animals; Mice; Diazooxonorleucine; Glutamine; Neoplasms; CD8-Positive T-Lymphocytes
PubMed: 37341499
DOI: 10.4049/jimmunol.2200715 -
Food and Chemical Toxicology : An... Aug 2023Azo dyes, including Tartrazine, Sunset Yellow, and Carmoisine, are added to foods to provide color, but they have no value with regard to nutrition, food preservation,... (Review)
Review
Azo dyes, including Tartrazine, Sunset Yellow, and Carmoisine, are added to foods to provide color, but they have no value with regard to nutrition, food preservation, or health benefits. Because of their availability, affordability, stability, and low cost, and because they provide intense coloration to the product without contributing unwanted flavors, the food industry often prefers to use synthetic azo dyes rather than natural colorants. Food dyes have been tested by regulatory agencies responsible for guaranteeing consumer safety. Nevertheless, the safety of these colorants remains controversial; they have been associated with adverse effects, particularly due to the reduction and cleavage of the azo bond. Here, we review the features, classification, regulation, toxicity, and alternatives to the use of azo dyes in food.
Topics: Azo Compounds; Tartrazine; Coloring Agents; Food; Food Industry; Food Coloring Agents
PubMed: 37429408
DOI: 10.1016/j.fct.2023.113935 -
Journal of Ethnopharmacology Jan 2024YangXueQingNaoWan (YXQNW), a compound Chinese medicine, has been widely used for dizziness, irritability, insomnia, and dreaminess caused by blood deficiency and liver...
ETHNOPHARMACOLOGICAL RELEVANT
YangXueQingNaoWan (YXQNW), a compound Chinese medicine, has been widely used for dizziness, irritability, insomnia, and dreaminess caused by blood deficiency and liver hyperactivity in China. However, whether YXQNW can inhibit cerebral microvascular exudation and cerebral hemorrhage (CH) caused by blood brain barrier (BBB) damage after tissue plasminogen activator (tPA) still unknown.
AIM OF THE RESEARCH
To observe the effect of YXQNW on cerebral microvascular exudation and CH after tPA and investigate its mechanism in protecting BBB.
MATERIALS AND METHODS
Male C57BL/6 N mice suffered from ischemia stroke by mechanical detachment of carotid artery thrombi with the stimulation of ferric chloride. Then mice were treated with tPA (10 mg/kg) and/or YXQNW (0.72 g/kg) at 4.5 h. Cerebral blood flow (CBF), infarct size, survival rate, neurological scores, gait analysis, Evans blue extravasation, cerebral water content, fluorescein isothiocyanate-labeled albumin leakage, hemorrhage, junction and basement membrane proteins expression, leukocyte adhesion and matrix metalloproteinases (MMPs) expression were evaluated 24 h after tPA. Proteomics was used to identify target proteins.
RESULTS
YXQNW inhibited cerebral infarction, neurobehavioral deficits, decreased survival, Evans blue leakage, albumin leakage, cerebral water content and CH after tPA thrombolysis; improved CBF, low-expression and degradation of junction proteins, basement membrane proteins, Arhgap21 and its downstream α-catenin and β-catenin proteins expression; and suppressed the increase of adherent leukocytes and the release of MMP-9 derived from macrophage.
CONCLUSION
YXQNW relieved BBB damage and attenuated cerebral microvascular exudation and CH after tPA thrombolysis. The effect of YXQNW on cerebral microvascular exudation was associated with the inhibition of the low-expression of junction proteins, especially AJs mediated by Rho GTPase-activating protein 21 (Arhgap21), while the effect on CH was associated with the inhibition of leukocyte adhesion, the release of MMP-9 derived from macrophage, and low-expression and degradation of collagen IV and laminin in the vascular basement membrane.
Topics: Male; Mice; Animals; Tissue Plasminogen Activator; Blood-Brain Barrier; Matrix Metalloproteinase 9; Evans Blue; Brain Ischemia; Mice, Inbred C57BL; Cerebral Hemorrhage; Cerebral Infarction; Ischemic Stroke; Thrombolytic Therapy; Albumins; Stroke
PubMed: 37572928
DOI: 10.1016/j.jep.2023.117024 -
Phytomedicine : International Journal... Dec 2023Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD), resulting from long-term inflammation in the intestines. The...
BACKGROUND
Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD), resulting from long-term inflammation in the intestines. The primary cause of CAC is the imbalance of oxidative metabolism in intestinal cells, triggered by excessive reactive oxygen (ROS) and nitrogen (NO) species production due to prolonged intestinal inflammation. This imbalance leads to genomic instability caused by DNA damage, eventually resulting in the development of intestinal cancer. Previous studies have demonstrated that astragaloside IV is effective in treating dextran sulfate sodium salt (DSS)-induced colitis, but there is currently no relevant research on its efficacy in treating CAC.
METHODS
To investigate the effect of astragaloside IV against CAC and the underlying mechanism, C57 mice were treated with (20, 40, 80 mg/kg) astragaloside IV while CAC was induced by intraperitoneal injection of 10 mg/kg azoxymethane (AOM) and ad libitum consumption of 2% dextran sulfate sodium salt (DSS). We re-verified the activating effects of astragaloside IV on PPARγ signaling in IEC-6 cells, which were reversed by GW9662 (the PPARγ inhibitor).
RESULTS
Our results showed that astragaloside IV significantly improved AOM/DSS-induced CAC mice by inhibiting colonic shortening, preventing intestinal mucosal damage, reducing the number of tumors and, the expression of Ki67 protein. In addition, astragaloside IV could activate PPARγ signaling, which not only promoted the expression of Nrf2 and HO-1, restored the level of SOD, CAT and GSH, but also inhibited the expression of iNOS and reduced the production of NO in the intestine and IEC-6 cells. And this effect could be reversed by GW9662 in vitro. Astragaloside IV thus decreased the level of ROS and NO in the intestinal tract of mice, as well as reduced the damage of DNA, and therefore inhibited the occurrence of CAC.
CONCLUSION
Astragaloside IV can activate PPARγ signaling in intestinal epithelial cells and reduces DNA damage caused by intestinal inflammation, thereby inhibiting colon tumourigenesis. The novelty of this study is to use PPARγ as the target to inhibit DNA damage to prevent the occurrence of CAC.
Topics: Animals; Mice; PPAR gamma; Azoxymethane; Dextran Sulfate; Reactive Oxygen Species; Colitis; Inflammation; Carcinogenesis; Cell Transformation, Neoplastic; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37776619
DOI: 10.1016/j.phymed.2023.155116 -
Environmental Research Dec 2023Due to their widespread application in water purification, there is a significant interest in synthesising nanoscale photocatalysts. Nanophotocatalysts are primarily... (Review)
Review
Due to their widespread application in water purification, there is a significant interest in synthesising nanoscale photocatalysts. Nanophotocatalysts are primarily manufactured through chemical methods, which can lead to side effects like pollution, high-energy usage, and even health issues. To address these issues, "green synthesis" was developed, which involves using plant extracts as reductants or capping agents rather than industrial chemical agents. Green fabrication has the benefits of costs less, pollution reduction, environmental protection and human health safety, compared to the traditional methods. This article summarises recent advances in the environmentally friendly synthesis of various nanophotocatalysts employed in the degradation of azo dyes. This study compiles critical findings on natural and artificial methods to achieve the goal. Green synthesis is constrained by the time and place of production and issues with low purity and poor yield, reflecting the complexity of plants' geographical and seasonal distributions and their compositions. However, green photocatalyst synthesis provides additional growth opportunities and potential uses.
Topics: Humans; Azo Compounds; Plant Extracts; Coloring Agents
PubMed: 37769832
DOI: 10.1016/j.envres.2023.117202 -
Chemphyschem : a European Journal of... Sep 2023Photochromic molecules can undergo a reversible conversion between two isomeric forms upon exposure to external stimuli such as electromagnetic radiation. A significant...
Photochromic molecules can undergo a reversible conversion between two isomeric forms upon exposure to external stimuli such as electromagnetic radiation. A significant physical transformation accompanying the photoisomerization process defines them as photoswitches, with potential applications in various molecular electronic devices. As such, a detailed understanding of the photoisomerization process on surfaces and the influence of the local chemical environment on switching efficiency is essential. Herein, we use scanning tunneling microscopy to observe the photoisomerization of 4-(phenylazo)benzoic acid (PABA) assembled on Au(111) in kinetically constrained metastable states guided by pulse deposition. Photoswitching is observed at low molecular density and is absent in tight-packed islands. Furthermore, switching events were noted in PABA molecules coadsorbed in a host octanethiol monolayer, suggesting an influence of the surrounding chemical environment on photoswitching efficiency.
PubMed: 37369072
DOI: 10.1002/cphc.202300160 -
Cell Reports Mar 2024The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility of radiotherapy. Here, we find that fecal microbiota transplantation (FMT)...
The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility of radiotherapy. Here, we find that fecal microbiota transplantation (FMT) potentiates the tumoricidal effects of radiation and degrades the intertwined adverse events in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. FMT cumulates Roseburia intestinalis (R. intestinalis) in the gastrointestinal tract. Oral gavage of R. intestinalis assembles at the CRC site and synthetizes butyrate, sensitizing CRC to radiation and alleviating intestinal toxicity in primary and CRC hepatic metastasis mouse models. R. intestinalis-derived butyrate activates OR51E1, a G-protein-coupled receptor overexpressing in patients with rectal cancer, facilitating radiogenic autophagy in CRC cells. OR51E1 shows a positive correlation with RALB in clinical rectal cancer tissues and CRC mouse model. Blockage of OR51E1/RALB signaling restrains butyrate-elicited autophagy in irradiated CRC cells. Our findings highlight that the gut commensal bacteria R. intestinalis motivates radiation-induced autophagy to accelerate CRC cell death through the butyrate/OR51E1/RALB axis and provide a promising radiosensitizer for CRC in a pre-clinical setting.
Topics: Humans; Animals; Mice; Butyrates; Clostridiales; Azoxymethane; Colorectal Neoplasms; Rectal Neoplasms; Dextran Sulfate; Disease Models, Animal; Mice, Inbred C57BL; Receptors, G-Protein-Coupled
PubMed: 38412097
DOI: 10.1016/j.celrep.2024.113846 -
Journal of Agricultural and Food... Oct 2023The research and development of organofluorine chemistry has flourished; in particular, monofluoroalkene has aroused considerable interest from medicinal and organic...
The research and development of organofluorine chemistry has flourished; in particular, monofluoroalkene has aroused considerable interest from medicinal and organic chemists. It is a significant attempt to introduce monofluoroalkene into agrochemicals. In this study, monofluoroalkene was introduced into diamide molecules and inserted between the aliphatic amide and benzene ring, and 44 compounds have been successfully synthesized. The bioassay results showed that compounds with monofluoro-acrylamide moiety (-isomers) had excellent larvicidal activity against lepidopteran pests at 5 mg·L. The LC values of compounds , , and against were 1.02, 1.32, and 0.78 mg·L, respectively. 3D-QSAR analysis including the CoMFA model and the CoMSIA model was conducted to illustrate the contributions of steric, electrostatic, hydrophobic, and hydrogen bond fields on the bioactivity. Moreover, typical symptoms caused by chlorantraniliprole including dehydration, shrinkage, and blackening were also observed on the test larvae treated with monofluoro-acrylamide diamide compounds. central neurons calcium imaging experiment of compound indicated that the monofluoro-acrylamide diamide compounds were potential insect ryanodine receptor activators. The molecular docking was performed in the CHL binding domain of RyR and revealed that the predicted binding mode of compound was slightly different from that of CHL. The MM|GBSA dG Bind values of and CHL with RyR were respectively -85.797 and -95.641 kcal·mol. The present work explored the insecticidal properties of a new diamide scaffold containing a monofluoro-acrylamide fragment and extended the application of monofluoroalkene in the agrochemical field.
Topics: Animals; Ryanodine Receptor Calcium Release Channel; Diamide; Acrylamides; Molecular Docking Simulation; Moths; Insecticides; Acrylamide; ortho-Aminobenzoates
PubMed: 37733789
DOI: 10.1021/acs.jafc.3c02737 -
ChemPlusChem Feb 2024This work reports the design and synthesis of novel oxadiazole-decorated azobenzenes, structural analysis of the resulting compounds and behavior under light...
This work reports the design and synthesis of novel oxadiazole-decorated azobenzenes, structural analysis of the resulting compounds and behavior under light irradiation. The synthetic strategy involved constructing amino functionalized heterocyclic key intermediates which were used either to yield electrophilic diazonium salts able to react with phenol moieties or as nucleophilic partners in Bayer-Mills reaction with nitroso-substituted derivatives. The amino-derived oxadiazole intermediates were investigated by absorption and emission spectroscopy providing blue and green emitted light. The target oxadiazole-decorated azobenzenes were structurally characterized, including solid-state structures, and subsequently used in irradiation experiments in order to take advantage of the azo group known to provide photoswitching abilities. We noticed quenching of the emissive properties in presence of the azo group; however, all compounds were very stable to repeated cycles of light irradiation. In addition, according to structural diversification we could obtain half-lives of the meta stable isomers within hours to hundreds of hours range. The experimental results were very well correlated with DFT calculations.
PubMed: 37882979
DOI: 10.1002/cplu.202300504 -
Journal of Hazardous Materials Jan 2024Tartrazine (TZ), or E 102 or C Yellow, is a commonly used azo dye in the food and dyeing industries. Its excessive usage beyond permissible levels threatens human health...
Tartrazine (TZ), or E 102 or C Yellow, is a commonly used azo dye in the food and dyeing industries. Its excessive usage beyond permissible levels threatens human health and the aquatic environment. While previous studies have reported adverse effects such as mutagenicity, carcinogenicity, and reproductive toxicity. Our study aimed to comprehensively evaluate the developmental neurotoxicity of TZ exposure via biochemical and behavioral examinations and explored the underlying mechanism via gene expression analyses. TZ at an environmentally relevant concentration (50 mg/L) significantly induces oxidative stress, altered antioxidant (SOD, CAT and GSH) response, triggered cellular damage (MDA and LDH), and induced neuro-biochemical changes (AChE and NO). Gene expression analyses revealed broad disruptions in genes associated with antioxidant defense (sod1, cat, and gstp1), mitochondrial dysfunction (mfn2, opa1, and fis1),evoked inflammatory response (nfkb, tnfa, and il1b), apoptosis activation (bcl2, bax, and p53), and neural development (bdnf, mbp, and syn2a). Behavioral analysis indicated altered thigmotaxis, touch response, and locomotion depending on the concentration of TZ exposure. Remarkably, the observed effective concentrations were consistent with the permitted levels in food products, highlighting the neurodevelopmental effects of TZ at environmentally relevant concentrations. These findings provide valuable insights into the underlying molecular mechanisms, particularly the role of mitochondria-mediated apoptosis, contributing to TZ-induced neurodevelopmental disorders in vivo.
Topics: Animals; Humans; Tartrazine; Antioxidants; Zebrafish; Azo Compounds; Oxidative Stress; Apoptosis; Mitochondria; Embryo, Nonmammalian
PubMed: 37741213
DOI: 10.1016/j.jhazmat.2023.132524