RESUMO
N-acetylcysteine (NAC) positively contributes to enhancing animal health, regulating inflammation and reducing stress by participating in the synthesis of cysteine, glutathione, and taurine in the body. The present study aims to investigate the effects of dietary different levels of NAC on the morphology, function and physiological state of hepatopancreas in juvenile common carp (Cyprinus carpio). 450 common carps were randomly divided into 5 groups: N1 (basal diet), N2 (1.5 g/kg NAC diet), N3 (3.0 g/kg NAC diet), N4 (4.5 g/kg NAC diet) and N5 (6.0 g/kg NAC diet), and fed for 8 weeks. The results indicated that dietary 3.0-6.0 g/kg NAC reduced hepatopancreas lipid vacuoles and nuclear translocation, and inhibited apoptosis in common carp. Simultaneously, the activities of hepatopancreas alanine aminotransferase and aspartate aminotransferase progressively increased with rising dietary NAC levels. Dietary NAC enhanced the non-specific immune function of common carp, and exerted anti-inflammatory effects by inhibiting the MAPK/NF-κB signaling pathway. Additionally, dietary 3.0-6.0 g/kg NAC significantly improved the antioxidant capacity of common carp, which was associated with enhanced glutathione metabolism, clearance of ROS and the activation of Nrf2 signaling pathway. In summary, NAC has the potential to alleviate inflammation, mitigate oxidative stress and inhibit apoptosis via the MAPK/NF-κB/Nrf2 signaling pathway, thereby improving hepatopancreas function and health of common carp. The current findings provide a theoretical basis for promoting the application of NAC in aquaculture and ecological cultivation of aquatic animals.
Assuntos
Antioxidantes , Carpas , Animais , Antioxidantes/metabolismo , NF-kappa B/metabolismo , Acetilcisteína/farmacologia , Carpas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopâncreas/metabolismo , Transdução de Sinais , Dieta/veterinária , Inflamação/veterinária , Glutationa , Suplementos NutricionaisRESUMO
This study aimed to evaluate the effects of varying zinc (Zn) levels on the growth performance, non-specific immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii (P. clarkii)). Adopting hydroxy methionine zinc (Zn-MHA) as the Zn source, 180 healthy crayfish with an initial body mass of 6.50 ± 0.05 g were randomly divided into the following five groups: X1 (control group) and groups X2, X3, X4, and X5, which were fed the basal feed supplemented with Zn-MHA with 0, 15, 30, 60, and 90 mg kg-1, respectively. The results indicated that following the addition of various concentrations of Zn-MHA to the diet, the following was observed: Specific growth rate (SGR), weight gain rate (WGR), total protein (TP), total cholesterol (TC), the activities of alkaline phosphatase (AKP), phenoloxidase (PO), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT), the expression of CTL, GPX, and CuZn-SOD genes demonstrated a trend of rising and then declining-with a maximum value in group X4-which was significantly higher than that in group X1 (P < 0.05). Zn deposition in the intestine and hepatopancreas, the activity of GSH-PX, and the expression of GSH-PX were increased, exhibiting the highest value in group X5. The malonaldehyde (MDA) content was significantly reduced, with the lowest value in group X4, and the MDA content of the Zn-MHA addition groups were significantly lower than the control group (P < 0.05). In the analysis of the intestinal microbiota of P. clarkii, the number of operational taxonomic units in group X4 was the highest, and the richness and diversity indexes of groups X3 and X4 were significantly higher than those in group X1 (P < 0.05). Meanwhile, the dietary addition of Zn-MHA decreased and increased the relative abundance of Proteobacteria and Tenericutes, respectively. These findings indicate that supplementation of dietary Zn-MHA at an optimum dose of 60 mg kg-1 may effectively improve growth performance, immune response, antioxidant capacity, and intestinal microbiota richness and species diversity in crayfish.
Assuntos
Antioxidantes , Microbioma Gastrointestinal , Animais , Antioxidantes/metabolismo , Metionina/metabolismo , Astacoidea/metabolismo , Zinco/farmacologia , Suplementos Nutricionais/análise , Dieta/veterinária , Racemetionina/farmacologia , Imunidade Inata , Superóxido Dismutase/farmacologia , Ração Animal/análiseRESUMO
Selenium (Se) is an essential nutrient element in human physiological metabolism and immune function. Supplementation of bioavailable Se will confer benefit on human life, especially when intake of this nutrient is inadequate. The edible and medicinal mushroom Antrodia camphorata is a unique fungus endemic to Taiwan, which has shown high therapeutic and nutritive value. This study is the first to demonstrate that A. camphorata can assimilate and transform sodium selenite into organic selenium. With an initial concentration of Se (IV) at 10 mg/L in 100 mL of the medium at 25 °C, the total selenium content in Se-enriched A. camphorata mycelia was 1281.3 ± 79.2 µg/g, in which the organic selenium content accounted for 88.1%. Further analysis demonstrated that selenium-enriched polysaccharide was the main form of Se present in A. camphorata (61.5% of the organic selenium). Four water-soluble Se-polysaccharide fractions were separated from A. camphorata, and ACP II was the major fraction of Se-polysaccharide. The scavenging efficiency of Se-polysaccharides on DPPH and ABTS radicals was determined, proving that selenium enrichment dramatically improved the in vitro antioxidant capacity of A. camphorata polysaccharide. Therefore, the selenium accumulation and transformation ability of A. camphorata provides an opportunity for developing this beneficent fungus into a novel selenium-enriched dietary or medicinal supplement.
Assuntos
Agaricales , Antrodia , Selênio , Humanos , Selênio/metabolismo , Fermentação , Polissacarídeos/química , Antrodia/químicaRESUMO
ARID1A, a component of the SWI/SNF chromatin remodeling complex, is a tumor suppressor with a high frequency of inactivating mutations in many cancers. Therefore, ARID1A deficiency has been exploited therapeutically for treating cancer. Here we show that ARID1A has a synthetic lethal interaction with aurora kinase A (AURKA) in colorectal cancer (CRC) cells. Pharmacological and genetic perturbations of AURKA selectively inhibit the growth of ARID1A-deficient CRC cells. Mechanistically, ARID1A occupies the AURKA gene promoter and negatively regulates its transcription. Cells lacking ARID1A show enhanced AURKA transcription, which leads to the persistent activation of CDC25C, a key protein for G2/M transition and mitotic entry. Inhibiting AURKA activity in ARID1A-deficient cells significantly increases G2/M arrest and induces cellular multinucleation and apoptosis. This study shows a novel synthetic lethality interaction between ARID1A and AURKA and indicates that pharmacologically inhibiting the AURKA-CDC25C axis represents a novel strategy for treating CRC with ARID1A loss-of-function mutations.
Assuntos
Aurora Quinase A/metabolismo , Neoplasias Colorretais/genética , Proteínas Nucleares/deficiência , Transdução de Sinais , Mutações Sintéticas Letais/genética , Fatores de Transcrição/deficiência , Fosfatases cdc25/metabolismo , Animais , Apoptose , Aurora Quinase A/antagonistas & inibidores , Aurora Quinase A/genética , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA , Avaliação Pré-Clínica de Medicamentos , Feminino , Fase G2 , Técnicas de Inativação de Genes , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitose , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
OBJECTIVE: To evaluate anti-melanoma effect of ethanol extract of Ilex hainanensis Merr. (IME) and elucidate its underlying mechanism. METHODS: Thirty-six tumor-bearing mice were randomized into 6 groups (n=6) as follows: model group, IME 25, 50, 100, and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25, 50, 100 or 200 mg/kg per day, respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-(4,5-dime-thylthylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 (NF-κB-p65), Bcl-2, B-cell lymphomaextra large (Bcl-xL) and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3, -8, and -9 activities were detected using the colorimetric method. In addition, a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore, a survival experiment of tumor-bearing mice was also performed to evaluate the possible toxicity of IME. RESULTS: IME significantly inhibited the proliferation of B16-F10 cells (P<0.01). Flow cytometric analysis showed that IME induced G1/S cell cycle arrest and apoptosis (both P<0.01). IME inhibited activation of NF-κB, decreased the gene and protein expressions of Bcl-2, Bcl-xL, and increased the gene and protein expressions of Bax (all P<0.01). In addition, IME induced the activation of Caspases-3, -8, and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume (P<0.01), and the inhibitory rate came up to 68.62%. IME also induced large areas of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor volume. Survival experiment showed that treatment with IME for 14 days significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group were still alive until the 50th day. Notably, IME showed no apparent side-effects during the treatment period. CONCLUSION: IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.