scholarly journals β-Conglycinin regulates distal intestinal immunity through the CIITA-mediated MHC II-PI3K/Akt/mTOR signaling pathway in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂): The ameliorative effects of sodium butyrate (NaB)

2020 ◽  
Author(s):  
Bin Yin ◽  
Hongyu Liu ◽  
Beiping Tan ◽  
Xiaohui Dong ◽  
Shuyan Chi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Performance ◽  
Sodium Butyrate ◽  
Intestinal Tract ◽  
Mtor Pathway ◽  
Mrna Levels ◽  
Mhc Ii ◽  
Epinephelus Fuscoguttatus ◽  
High Doses ◽  
High Level

Abstract Background β-Conglycinin (7S) is a strong immunogenic protein that modulates immune responses in the intestines of aquatic animals, whereas sodium butyrate (NaB) may promote growth by protecting the intestinal tract of fish. However, the mechanisms of action of 7S and NaB in these regards have yet to be determined. Results In this study, we investigated the effects of low and high doses of 7S and the ameliorative effects of NaB (based on high-dose 7S) on the growth performance, serum immunity, distal histopathology, and CIITA-mediated MHC II-PI3K/Akt/mTOR pathway in hybrid groupers (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). The results revealed that the specific growth rate of groupers significantly increased, decreased, and increased in the low-level 7S (bL), high-level 7S (bH) high-level 7S plus NaB (bH-NaB) groups, respectively. The feed coefficient ratio was significantly increased in the bH and bH-NaB groups, whereas serum levels of IgE, IFN-γ, IL-1β, and TNF-α were upregulated in the bH group, and IgE was upregulated in the bH-NaB group. With respect to distal intestine histopathology, the intestinal diameter/plica height ratio was significantly increased in the bH group. Furthermore, there were increases in nitric oxide, nitric oxide synthase (NOS), and peroxynitrite anion (ONOO) in the bH group, and decreases in NOS and ONOO in the bH-NaB group In the distal intestinal tract, the mRNA levels of TSC1, mTOR C2, CIITA, and CREB1 were significantly upregulated in all three treatment groups, whereas those of IKKα, Rheb, mTOR C1, mLST8, EIF4B, NFY, GILT, and AEP were upregulated and downregulated in the bH and bH-NaB groups, respectively. Conclusions Collectively, these results indicate that 7S has a regulatory effect on serum immunity and can also affect distal intestinal tract development in hybrid groupers by modulating hindgut injury-related parameters. Within the distal intestinal tract, 7S can induce intestinal inflammation by activating the CIITA-mediated MHC II-PI3K/Akt/mTOR pathway, which eventually manifests as a reduction in growth performance. Supplementing feed with NaB represents an effective approach for enhancing serum immunity, and also protects the intestines from damage caused by high doses of 7S.

scholarly journals Effects of Low- and High-Level Gossypol and Sodium Butyrate Supplementation Under High-Level Gossypol Condition on Growth Performance and Intestinal Health of Hybrid Grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂)

2021 ◽  
Vol 8 ◽  
Author(s):  
Bin Yin ◽  
Hongyu Liu ◽  
Beiping Tan ◽  
Xiaohui Dong ◽  
Shuyan Chi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Performance ◽  
Tight Junctions ◽  
Sodium Butyrate ◽  
Feed Utilization ◽  
Mrna Levels ◽  
Intestinal Health ◽  
Hybrid Grouper ◽  
Epinephelus Fuscoguttatus ◽  
High Level

The supplementation of gossypol in excess is noted to cause detrimental effects such as the reduction of antioxidant enzymes and disruption of lipid metabolism in animals. Studies regarding the effects of different levels of gossypol are very rare; thus, this study was conducted to evaluate the effects of low and high dietary levels of gossypol and of supplementation with 0.13 % sodium butyrate (NaB) under high gossypol conditions on the growth performance and intestinal health of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂). Four treatments were used: Feed containing 40% fish meal was used as the control group [fishmeal (FM)], the FM diet plus 0.03% gossypol acetic acid (abbreviated as gossypol) as the low-level gossypol group (gL), FM + 0.15% gossypol was used as the high-level gossypol group (gH), and FM+0.15 % gossypol with 0.13 % NaB as the repair group (gHNaB). All diets were isonitrogenous and isolipidic. The results showed that the gL treatment significantly increased specific growth rate (SGR) and feed utilization; upregulated mRNA levels of distal intestinal transforming growth factor-β1 (tgfβ1), jam, occludin, claudin3, and zo1; and downregulated mRNA levels of il8, ifnγ, and akt. The gH treatment significantly reduced SGR and feed utilization; increased distal intestinal total nitric oxide synthase (NOS) activity and nitric oxide (NO) content; upregulated mRNA levels of distal intestinal tnfα, il1β, il6, ifnγ, caspase2, caspase9, and akt; and downregulated mRNA levels of tgfβ1, jam, and zo1. NaB supplementation significantly increased distal intestinal total NOS activity and NO content; downregulated distal intestinal tnfα, il1β, ifnγ, pi3k p85, and akt mRNA levels; and increased distal intestinal tgfβ1, jam, occludin, and zo1 mRNA levels. Above all, low- and high-level gossypol exhibited positive and negative effects on growth performance, distal intestinal anti-inflammatory capacity, and tight junctions, respectively, in hybrid groupers. NaB supplementation improved distal intestinal anti-inflammatory capacity and tight junctions in hybrid groupers to a certain extent.

scholarly journals β-Conglycinin Regulates Intestinal Immunity through the CIITA-mediated MHC II-PI3K/Akt/mTOR Pathway in Hybrid Grouper: The Ameliorative Effects of Sodium Butyrate (NaB)

2021 ◽  
Author(s):  
Bin Yin ◽  
Hongyu Liu ◽  
Beiping Tan ◽  
Xiaohui Dong ◽  
Shuyan Chi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Performance ◽  
Intestinal Inflammation ◽  
Mtor Pathway ◽  
High Dose ◽  
Mrna Levels ◽  
Intestinal Immunity ◽  
Mhc Ii ◽  
Hybrid Grouper ◽  
High Level

Abstract We investigated the effects of low and high doses of 7S and the ameliorative effects of NaB (based on high-dose 7S) on the growth performance, serum immunity, distal histopathology, and CIITA-mediated MHC II-PI3K/Akt/mTOR pathway in hybrid groupers. The results revealed that the specific growth rate of groupers significantly increased, decreased, and increased in the low-level 7S (bL), high-level 7S (bH) high-level 7S plus NaB (bH-NaB) groups, respectively. The feed coefficient ratio was significantly increased in the bH and bH-NaB groups, whereas serum levels of IFN-γ, IL-1β, and TNF-α were upregulated in the bH group. The intestinal diameter/plica height ratio was significantly increased in the bH group. Furthermore, there were increases in nitric oxide, nitric oxide synthase (NOS), and peroxynitrite anion (ONOO−) in the bH group, and decreases in NOS and ONOO− in the bH-NaB group. The mRNA levels in distal intestine of TSC1, mTOR C2, CIITA, and CREB1 were significantly upregulated in all three treatment groups, whereas those of IKKα, Rheb, mTOR C1, mLST8, EIF4B, NFY, GILT, and AEP were upregulated and downregulated in the bH and bH-NaB groups, respectively. These indicate 7S has a regulatory effect on serum immunity and affect distal intestinal development by modulating hindgut injury-related parameters. Within the distal intestinal tract, 7S can induce intestinal inflammation by activating the CIITA-mediated MHC II-PI3K/Akt/mTOR pathway, which eventually manifests as a reduction in growth performance. Supplementing feed with NaB represents an effective approach for enhancing serum immunity, and also protects the intestines from damage caused by high-dose 7S.

scholarly journals Dietary supplementation of β-conglycinin, with or without sodium butyrate on the growth, immune response and intestinal health of hybrid grouper

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bin Yin ◽  
Hongyu Liu ◽  
Beiping Tan ◽  
Xiaohui Dong ◽  
Shuyan Chi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Performance ◽  
Sodium Butyrate ◽  
High Dose ◽  
Mrna Levels ◽  
Distal Intestine ◽  
Hybrid Grouper ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level

AbstractWe investigated the effects of low and high doses of β-conglycinin and the ameliorative effects of sodium butyrate (based on high-dose β-conglycinin) on the growth performance, serum immunity, distal intestinal histopathology, and gene, protein expression related to intestinal health in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). The results revealed that the instantaneous growth rate (IGR) of grouper significantly increased, decreased, and increased in the low-dose β-conglycinin (bL), high-level β-conglycinin (bH) and high-level β-conglycinin plus sodium butyrate (bH-NaB), respectively. The feed coefficient ratio (FCR) was significantly increased in the bH and bH-NaB, serum levels of IFN-γ, IL-1β, and TNF-α were upregulated in the bH. The intestinal diameter/fold height ratio was significantly increased in the bH. Furthermore, there were increases in nitric oxide (NO), total nitric oxide synthase (total NOS), and peroxynitrite anion (ONOO−) in the bH, and decreases in total NOS and ONOO− in the bH-NaB. In the distal intestine, IL-1β and TGF-β1 mRNA levels were downregulated and upregulated, respective in the bL. The mRNA levels of TNF-α and IL-6 were upregulated in the bH, and downregulated in the bH-NaB, respectively. Occludin, claudin3 and ZO-3 mRNA levels were upregulated in the bL, downregulated in the bH and then upregulated in the bH-NaB. No significant differences were observed in the mRNA levels of IFN-γ and jam4. And the p-PI3K p85Tyr458/total PI3K p85 value was significantly increased in the bH and then decreased in the bH-NaB, and the total Akt value was significantly increased in the bH. These indicate β-conglycinin has a regulatory effect on serum immunity and affect distal intestinal development by modulating distal intestinal injury-related parameters. Within the distal intestinal tract, low- and high-dose β-conglycinin differentially affect immune responses and tight junctions in the distal intestine, which eventually manifests as a reduction in growth performance. Supplementing feed with sodium butyrate might represent an effective approach for enhancing serum immunity, and protects the intestines from damage caused by high-dose β-conglycinin.

scholarly journals MHC II-PI3K/Akt/mTOR Signaling Pathway Regulates Intestinal Immune Response Induced by Soy Glycinin in Hybrid Grouper: Protective Effects of Sodium Butyrate

2021 ◽  
Vol 11 ◽  
Author(s):  
Bin Yin ◽  
Hongyu Liu ◽  
Beiping Tan ◽  
Xiaohui Dong ◽  
Shuyan Chi ◽  
...  
Keyword(s):  
Sodium Butyrate ◽  
Low Dose ◽  
Intestinal Inflammation ◽  
Control Group ◽  
High Dose ◽  
Mrna Levels ◽  
Growth Ratio ◽  
Mhc Ii ◽  
Hybrid Grouper ◽  
Ifn Γ

Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1β were upregulated in the GH group. IgG, IL-1β, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PI3KSer294/T-PI3K, P-AktSer473/T-Akt, and P-mTORSer2448/T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1β is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PI3K and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PI3K/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.

scholarly journals Arginase Isoform Expression in Chronic Rhinosinusitis

2019 ◽  
Vol 8 (11) ◽  
pp. 1809 ◽  
Author(s):  
Diana Vlad ◽  
Silviu Albu
Keyword(s):  
Nitric Oxide ◽  
Chronic Rhinosinusitis ◽  
Defense Mechanisms ◽  
Upper Airway ◽  
Control Group ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Endoscopic View ◽  
Important Regulator ◽  
Arginase I

Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 ± 0.42 vs. 1.31 ± 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 ± 1.16 vs. 1.31 ± 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 ± 0.52 vs. 1.31 ± 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 ± 0.57 vs. 1.31 ± 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

scholarly journals Decrease post-transplant relapse using donor-derived expanded NK-cells

Leukemia ◽  
2021 ◽  
Author(s):  
Stefan O. Ciurea ◽  
Piyanuch Kongtim ◽  
Doris Soebbing ◽  
Prashant Trikha ◽  
Gregory Behbehani ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Disease Free Survival ◽  
Dependent Manner ◽  
Post Transplant ◽  
Haploidentical Transplantation ◽  
High Doses ◽  
High Level

AbstractIn this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 × 105–1 × 108 cells/kg/dose) were administered on days −2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database.After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% (p = 0.014), and disease-free survival (DFS) was 66% vs. 44% (p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 (p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype.Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 (https://clinicaltrials.gov/ct2/show/NCT01904136).

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