ABSTRACT
The optimal dietary vitamin C (VC) levels for walleye pollock (Gadus chalcogrammus) remain undefined. This study aimed to assess the effect of dietary VC levels on the growth performance and biochemical parameters of grower walleye pollock and determine the optimal VC level for their diet. Six experimental diets (VC0, VC1, VC3, VC5, VC7, and VC10) with VC levels of 3.24, 21.92, 63.31, 101.42, 145.46, and 202.51 mg kg-1 diet, respectively, were fed to fish (initial mean weight: 173.5 ± 0.31 g) for 8 weeks. At the end of the feeding trial, fish fed the VC7 and VC10 diets exhibited significantly higher growth (final body weight, weight gain, and specific growth rate) and improved feed utilization (feed efficiency and protein efficiency ratio) compared with fish fed the VC0 diet (p < 0.05). The VC3-VC10 diets significantly reduced plasma superoxide dismutase (SOD) activity (p < 0.05). Compared with the VC0 group, fish fed the VC7 and VC10 diets showed significantly elevated growth hormone and insulin-like growth factor-1 levels in plasma (p < 0.05). In conclusion, dietary VC supplementation in walleye pollock improved growth performance and SOD activity. Moreover, broken-line analysis on weight gain indicated that the optimal dietary VC level for grower walleye pollock was approximately 156.42 mg kg-1 diet.
ABSTRACT
Viral pathogens, particularly influenza and SARS-CoV-2, pose a significant global health challenge. Given the immunomodulatory properties of human milk oligosaccharides, in particular 2'-fucosyllactose and 3-fucosyllactose (3-FL), we investigated their dietary supplementation effects on antiviral responses in mouse models. This study revealed distinct immune modulations induced by 3-FL. RNA-sequencing data showed that 3-FL increased the expression of interferon receptors, such as Interferon Alpha and Beta Receptor (IFNAR) and Interferon Gamma Receptor (IFNGR), while simultaneously downregulating interferons and interferon-stimulated genes, an effect not observed with 2'-fucosyllactose supplementation. Such modulation enhanced antiviral responses in both cell culture and animal models while attenuating pre-emptive inflammatory responses. Nitric oxide concentrations in 3-FL-supplemented A549 cells and mouse lung tissues were elevated exclusively upon infection, reaching 5.8- and 1.9-fold increases over control groups, respectively. In addition, 3-FL promoted leukocyte infiltration into the site of infection upon viral challenge. 3-FL supplementation provided protective efficacy against lethal influenza challenge in mice. The demonstrated antiviral efficacy spanned multiple influenza strains and extended to SARS-CoV-2. In conclusion, 3-FL is a unique immunomodulator that helps protect the host from viral infection while suppressing inflammation prior to infection.
Subject(s)
Trisaccharides , Animals , Mice , Humans , Trisaccharides/pharmacology , Trisaccharides/immunology , A549 Cells , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/drug therapy , Female , SARS-CoV-2/immunology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , COVID-19/immunology , Mice, Inbred BALB C , Disease Models, Animal , Dietary Supplements , Nitric Oxide/metabolism , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Lung/immunology , Lung/virology , OligosaccharidesABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.