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1.
Nat Commun ; 15(1): 3480, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658537

RESUMEN

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity in Drosophila, Caenorhabditis elegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors for in vivo circuit analysis in behaving animals.


Asunto(s)
Caenorhabditis elegans , Neuronas , Optogenética , Pez Cebra , Animales , Caenorhabditis elegans/genética , Neuronas/metabolismo , Neuronas/fisiología , Optogenética/métodos , Channelrhodopsins/metabolismo , Channelrhodopsins/genética , Humanos , Drosophila , Canales de Potasio/metabolismo , Canales de Potasio/genética , Cloruros/metabolismo , Animales Modificados Genéticamente , Conducta Animal , Células HEK293 , Drosophila melanogaster
2.
Mol Immunol ; 166: 110-118, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38280829

RESUMEN

Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro. In this study, we constructed a chronic IBD mouse model and demonstrated the therapeutic effects of α-mangostin and its derivatives as therapeutic agents for IBD. In compounds treating groups, intestinal inflammation showed significant improvement in symptoms which included weight loss, high disease activity index, colon length shorten and the change of intestinal flora. We also found that compounds could effectively either suppress the number of Th17 cell or increase the number of Treg cell detected by flow cytometry, thus reducing the Th17/Treg ratio and suppressing the level of intestinal inflammation. Notably, IL17-F levels, rather than IL17-A, were reduced in the colon of mice of compounds treating groups. Thus, α-mangostin and its derivatives ameliorate DSS-induced chronic colitis in mice by regulating Th17/Treg balance to alleviate intestinal inflammation and can modulate the intestinal microbial community. These results suggest that α-mangostin and its derivatives may be the new therapeutic option for chronic colitis.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Xantonas , Ratones , Animales , Células Th17 , Linfocitos T Reguladores , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colon , Inflamación , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
3.
J Hazard Mater ; 170(1): 411-6, 2009 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-19467775

RESUMEN

Cerium supported on activated carbon (Ce/AC), which was prepared by dipping method, was employed to degrade dimethyl phthalate (DMP) in water. The mineral matter present in the activated carbon positively contributes to its activity to enhance DMP ozonation process. A higher dipping Ce(NO(3))(3) concentration and calcination process increase its microporous volume and surface area, and decreases its exterior surface area. The catalytic activity reaches optimal when 0.2% (w/w) cerium is deposited on activated carbon. Ce/AC catalyst was characterized by XRD, SEM and BET. The presence of either activated carbon or Ce/AC catalyst considerably improves their degradation and mineralization in the ozonation of DMP. During the ozonation (50mg/h ozone flow rate) of a 30 mg/L DMP (initial pH 5.0) with the presence of Ce/AC catalyst, TOC removal rate reaches 68% at 60 min oxidation time, 48% using activated carbon as catalyst, only 22% with ozonation alone. The presence of tert-butanol (a well known OH radical scavenger) strongly inhibits DMP degradation by activated carbon or Ce/AC catalytic ozonation. TOC removal rate follows the second-order kinetics model well. In the ozonation of DMP with 50mg/h ozone flow rate, its mineralization rate constant with the presence of Ce/AC catalyst is 2.5 times higher than that of activated carbon, 7.5 times higher than that of O(3) alone. Ce/AC catalyst shows the better catalytic activity and stability based on 780 min sequential reaction in the ozonation of DMP. Ce/AC was a promising catalyst for ozonizing organic pollutants in the aqueous solution.


Asunto(s)
Ozono/química , Ácidos Ftálicos/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Catálisis , Cerio , Carbón Orgánico , Depuradores de Radicales Libres/química , Cinética , Compuestos Orgánicos/química
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