Alternative Complement Activation Research Articles

Effects of Antrodia camphorata-Supplemented Diets on the Non-Specific Immune Responses and Disease Resistance of Orange-Spotted Grouper (Epinephelus coioides) against Vibrio alginolyticus and Streptococcus iniae

In Taiwan, the mushroom Antrodia camphorata (AC) is used for medicinal purposes, including cancer prevention and treatment. This study aimed to investigate the effect of AC-supplemented diets on the innate immunity and disease resistance of the orange-spotted grouper Epinephelus coioides against two bacterial infections—Vibrio alginolyticus and Streptococcus iniae. Orange-spotted groupers were fed AC-supplemented diets at 0 (control), 1.5, 3.0, 4.5, and 6.0 g kg−1 for 28 days and examined for innate immune responses and survival rates against V. alginolyticus and S. iniae. The results showed that the innate cellular and humoral immune parameters, including respiratory burst, phagocytic activity, and lysozyme activity of leukocytes, along with serum alternative complement activity (ACH50) and superoxide dismutase activity, as well as interleukin (IL)-4 and IL-6, were all significantly increased in groupers fed AC-supplemented diets. Groupers fed diets containing AC at doses higher than 3.0 g kg−1 had better survival rates than the control group 3–18 days after V. alginolyticus or S. iniae challenge. The enhanced disease resistance may be attributable to AC-induced innate immunity, suggesting that utilizing AC as a dietary supplement at 3.0 g kg−1 may enhance the disease resistance of orange-spotted groupers against Vibrio or Streptococcus infection.

Dietary Dracocephalum kotschyi essential oil improved growth, haematology, immunity and resistance to Aeromonas hydrophila in rainbow trout ( Oncorhynchus mykiss )

In the present study, the effect of Dracocephalum kotschyi essential oil (DKE) was investigated on growth, haematology, immune and antioxidant defence system and resistance of rainbow trout juveniles to bacterial infection (Aeromonas hydrophila). For this purpose, the fish were fed a diet containing different concentrations of DKE including 0 (control), 0.2, 0.25 and 0.3 mg/kg diet in three replicates for 60 days. After feeding trial, the fish were challenged with a pathogenic dose of A. hydrophila. Based on the results, immune components in plasma (alternative complement activity [ACH50], IgM content, lysozyme activity, total protein and total albumin) and mucus (protease activity, IgM content and lysozyme activity) significantly elevated in fish fed diet containing 0.2 and 0.25 mg DKE/kg diet compared with other groups (p < 0.01). The plasma bactericidal activity increased in all DKE-supplemented fish. Supplementation of fish with 0.3 mg DKE/kg diet depressed the mucosal lysozyme activity and IgM content. The liver antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) showed increased activity in response to 0.25 and 0.3 mg DKE/kg diet compared with other experimental diets (p < 0.01). Dietary DKE changed the haematology of the fish. The haematocrit, red blood cell count (RBC), white blood cell (WBC), haemoglobin content and mean erythrocyte cell haemoglobin content (MCHC) increased in response to DKE. In contrast, the mean corpuscular haemoglobin (MCH) decreased in fish fed 0.2 and 0.25 mg DKE/kg diet compared with other diets (p < 0.01). The supplementation of fish with 0.2 and 0.25 mg DKE/kg diet decreased the expression of cytokine-related genes, TNF-α and IL-8. In contrast, the DKE up-regulated the expression of the immune-related genes, C3 and lysozyme. DKE at concentration of 0.3 mg/kg diet depressed the C3 and lysozyme gene expressions. The DKE supplementation decreased the mortality rate of the fish after bacterial challenge compared with non-supplemented ones (p < 0.01). In conclusion, the findings of this study revealed the immune-stimulating effects of DKE at optimized dietary concentrations. In addition, DKE decreased the mortality induced by A. hydrophila infection.

Effect of Licorice (Glycyrrhiza glabra) Extract as an Immunostimulant on Serum and Skin Mucus Immune Parameters, Transcriptomic Responses of Immune-Related Gene, and Disease Resistance Against Yersinia ruckeri in Rainbow Trout (Oncorhynchus mykiss).

This study was designed to appraise the effect of licorice herbal supplement on the immune status of rainbow trout fingerlings. Accordingly, five diets were formulated with different levels of licorice extract (LE) including 0 (control), 0.5 g kg−1 (LE0.5), 1 g kg−1 (LE1), 2 g kg−1 (LE2), and 3 g kg−1 (LE3). The fingerlings (10.0 ± 0.1 g initial mean weight) received the diets in triplicates (30 fish in each replicate) for 56 days. The results showed that the white blood cells and their differential number (lymphocytes and monocytes) were remarkably increased by LE2 supplementation (P < 0.05). The oral administration of LE2 significantly increased the levels of serum immunoglobulin (Ig), lysozyme activity, and complement components (C3 and C4) compared with others. Meanwhile, the serum bactericidal activity against Yersinia ruckeri in LE2 and LE3 treatments was significantly higher than others except for LE1 (P < 0.05). In addition, serum alternative complement activity significantly improved in all treated groups except LE0.5 compared with the control group (P < 0.05). In terms of skin mucosal immunity, the fish fed with LE2 and LE3 diets exhibited notably higher lysozyme activity, alkaline phosphatase activity, and Ig value than other groups (P < 0.05). The highest skin mucus bactericidal activity against Y. ruckeri was obtained in LE2 treatment (P < 0.05). In addition, dietary LE2 significantly increased the relative expression of immune-associated genes including tumor necrosis factor-α, interleukin-1β, interleukin-8, and IgM and the former treatments showed higher values than the control group. The cumulative mortality of fish against Y. ruckeri infection was notably reduced from 53.6% in the control group to 29.0% in LE3 treatment. Overall, the dietary administration of LE at 2 g kg−1 had the best effects on immunocompetence in rainbow trout.

Chronic exposure to sublethal concentrations of saxitoxin reduces antioxidant activity and immunity in zebrafish but does not affect reproductive parameters

Saxitoxin produced by dinoflagellates and cyanobacteria can be transferred to humans through intoxicated organisms such as fish, but limited research has addressed the adverse effects of this toxin on aquatic organisms. In this study, we measured the potential effects of a 90-day exposure to saxitoxin (0.1 or 1 µg·L - 1) on body weight and length, antioxidant defense system, immunity, sex hormones, and genes involved in associated key metabolic pathways in zebrafish (Danio rerio). Significant impairments in body weight and length were observed in response to 1 µg·L - 1 saxitoxin in both male and female zebrafish. A significant increase in the levels of malondialdehyde, together with decreased enzymatic activities of catalase and superoxide dismutase, was observed in fish of both sexes exposed to 1 µg·L - 1 saxitoxin, indicating the occurrence of lipid peroxidation and oxidative stress. Immune parameters such as alternative complement activity, lysozyme activity, and immunoglobulin content were also significantly reduced. However, exposure of male and female zebrafish to saxitoxin for 90 days did not significantly affect reproductive parameters such as the gonadosomatic index and plasma concentrations of vitellogenin, estradiol, and 11-keto testosterone. Transcriptional responses showed similar trends to those of the biochemical parameters, as genes involved in the antioxidant defense system and immunity were downregulated, whereas the transcription of genes related to reproductive metabolism showed no significant change upon treatment with 1 µg·L - 1 saxitoxin. Our findings indicate that long-term exposure to a sublethal concentration of saxitoxin can inhibit growth through induction of oxidative stress and immunosuppression, while the reproductive parameters of zebrafish are not a main target of this toxin at sublethal concentrations.

Dietary glycine supplementation modulates antioxidant and immune responses of beluga, Huso huso, juveniles

Glycine is a non-essential amino acid used in fish nutrition, and possess several important roles in physiological process. Despite such functions, little is known about the glycine roles in fish, particularly in sturgeons. Therefore, the present study aimed at assessing the effects of dietary glycine supplementation on growth performance, antioxidant, and immunological parameters in beluga, Huso huso. Four hundred eighty fish (~ 48 g) were randomly distributed in 12 fiberglass tanks (1200 L) at a stocking density of 40 fish per tank. Four diets supplemented with 0% (control), 0.25% (Gly0.25), 0.5% (Gly0.5), and 1% (Gly1) glycine were offered to the fish (each diet to a batch of three tanks) for eight weeks at water temperature of 23.2 ± 0.70 °C. At the end of the feeding trial, the fish were blood-sampled for blood leukocyte count, plasma cortisol, glucose, triglyceride, cholesterol, reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA), lysozyme, and alternative complement activity (ACH50) analysis. The results indicated there were no significant differences in the fish final weight (197–213 g; P = 0.511), weight gain (299–311%; P = 0.956) specific growth rate (2.46–2.52%/d; P = 0.944), feed conversion ratio (0.97–1.03; P = 0.863), protein efficiency ratio (2.29–2.45; P = 0.775), and survival (91.7–100%; P = 0.306) among the treatments. Plasma cortisol level significantly decreased in Gly0.25 treatment, compared to the control (24.7 vs. 28.8 ng/mL; P = 0.035). Plasma glucose levels exhibited significant (P < 0.001) elevation in Gly0.5 (51.0 mg/dL) and Gly1 (53.0 mg/dL) treatments, compared to the control (42.0 mg/dL). The treatment Gly0.5 showed significant elevations in blood leukocyte count (11.4 vs. 8.23 ×1000cell/µL; P = 0.032), plasma triglyceride (581 vs. 410 mg/dL; P = 0.017), cholesterol (71.3 vs. 59.8 mg/dL; P = 0.011), GSH (2.67 vs. 2.21 mM/mL; P = 0.003), GPx (243 vs. 217 U/mL; P < 0.001), and MDA (123 vs. 99 mM/L; P < 0.001), compared to the control treatment. Plasma GR (P < 0.001) showed significant decrease in Gly0.5 (1154 vs. 1784 U/mL) and Gly1 (1171 vs. 1784 U/mL) treatments. Besides, Gly0.25 and Gly0.5 treatments showed significantly higher plasma lysozyme (45.8–45.9 vs. 36.5 U/mL; P = 0.001) and ACH50 (138–139 vs. 130 U/mL; P < 0.001), compared to the control. Based on the results, dietary glycine supplementation at 0.25–0.5% could suppress plasma cortisol levels and improve antioxidant and immunological parameters on beluga, although has no beneficial effects on the fish growth performance.

Environment-Dependent Heterosis and Transgressive Gene Expression in Reciprocal Hybrids between the Channel Catfish Ictalurus punctatus and the Blue Catfish Ictalurus furcatus

The hybrid between female channel catfish (Ictalurus punctatus) and male blue catfish (Ictalurus furcatus) is superior in feed conversion, disease resistance, carcass yield, and harvestability compared to both parental species. However, heterosis and heterobeltiosis only occur in pond culture, and channel catfish grow much faster than the other genetic types in small culture units. This environment-dependent heterosis is intriguing, but the underlying genetic mechanisms are not well understood. In this study, phenotypic characterization and transcriptomic analyses were performed in the channel catfish, blue catfish, and their reciprocal F1s reared in tanks. The results showed that the channel catfish is superior in growth-related morphometrics, presumably due to significantly lower innate immune function, as investigated by reduced lysozyme activity and alternative complement activity. RNA-seq analysis revealed that genes involved in fatty acid metabolism/transport are significantly upregulated in channel catfish compared to blue catfish and hybrids, which also contributes to the growth phenotype. Interestingly, hybrids have a 40-80% elevation in blood glucose than the parental species, which can be explained by a phenomenon called transgressive expression (overexpression/underexpression in F1s than the parental species). A total of 1140 transgressive genes were identified in F1 hybrids, indicating that 8.5% of the transcriptome displayed transgressive expression. Transgressive genes upregulated in F1s are enriched for glycan degradation function, directly related to the increase in blood glucose level. This study is the first to explore molecular mechanisms of environment-dependent heterosis/heterobeltiosis in a vertebrate species and sheds light on the regulation and evolution of heterosis vs. hybrid incompatibility.

Dietary Guduchi (Tinospora cordifolia) enhanced the growth performance, antioxidative capacity, immune response and ameliorated stress-related markers induced by hypoxia stress in Nile tilapia (Oreochromis niloticus)

Nile tilapia can tolerate a wide range of farming conditions; however, fluctuations in the environmental conditions may impair their health status. The incorporation of medicinal herbs in aquafeed is suggested to overcome stressful conditions. In this study, dietary Guduchi (Tinospora cordifolia) was evaluated on the growth performance, antioxidative capacity, immune response, and resistance of Nile tilapia against hypoxia stress. Fish fed five diets incorporated with Guduchi at 0, 2, 4, 6, and 8 g/kg for 56 days then exposed with hypoxia stress for 72 h. The growth performance, feed intake, and feed efficiency ratio were significantly (P < 0.05) increased by including Guduchi in tilapia diets regardless of the inclusion level. Similarly, the lipase and protease activities were markedly (P < 0.05) increased in tilapia fed dietary Guduchi. The activities of lysozyme and bactericidal activities in serum and mucus, nitro-blue tetrazolium (NBT), and alternative complement activity (ACH50) were markedly (P < 0.05) enhanced in tilapia treated with Guduchi supplements regardless of the dose. Additionally, the activities of liver and intestinal superoxide dismutase, catalase, and glutathione peroxidase were markedly enhanced (P < 0.05) by including Guduchi in tilapia diets compared with the control. Before and after hypoxia stress, tilapia-fed dietary Guduchi had lower glucose and cortisol levels than fish-fed Guduchi-free diets (P < 0.05). In all groups, glucose and cortisol levels were markedly higher after hypoxia compared before hypoxia stress (P < 0.05). In conclusion, dietary Guduchi can be included at 5.17–5.49 g/kg to enhance the growth performance, digestive enzyme activity, immune and antioxidative responses, and the resistance of Nile tilapia against hypoxia stress.

Impacts of Amla (Phyllanthus emblica) fruit extract on growth, skin mucosal and serum immunities, and disease resistance of Nile tilapia (Oreochromis niloticus) raised under biofloc system

This study aimed to investigate the effects of Amla (Phyllanthus emblica) fruit extract (AFE) on the growth, skin mucosal and serum immunity, and disease resistance of Nile tilapia (Oreochromis niloticus) against Streptococcus agalactiae. Three hundred fish (10.48 ± 0.56 g fish-1) were distributed in 15 tanks with 20 fish per tank and fed basal diet supplemented with 0, 5, 10, 20, and 40 mg kg-1 AFE for eight weeks. The completed randomized design with three replications was applied. Growth performance, peroxidase, alternative complement, phagocytosis, and respiratory burst activities were determined at weeks 4 and 8. The challenge study was conducted at the end of the experiment. Based on the results, Nile tilapia fed the AFE diets significantly enhanced skin mucus lysozyme and peroxidase activities (P ≤ 0.05) post-feeding. The highest levels were observed in the group that received 20 mg kg-1 of AFE (P ≤ 0.05), whereas the control group presented the lowest levels of lysosome and peroxidase activities. Similarly, incorporation of 20 mg kg-1 of AFE brought about the maximum levels of (P ≤ 0.05) serum lysozyme, peroxidase, alternative complement, phagocytosis, and respiratory burst activities in contrast to the other treatments; whereas fish fed the control diet generated the lowest immune parameter values (P ≤ 0.05). In the challenge study, the Nile tilapia’s relative percent survival (RPS) was 52.38%, 61.90%, 80.95%, and 47.62% in Diet 2, Diet 3, Diet 4, and Diet 5, respectively. Fish fed 20 mg kg-1 AFE showed significantly (P < 0.05) higher RPS, as well as the highest resistance towards S. agalactiae. The inclusion of AFE for 8 weeks resulted in a significant (P < 0.05) enhancement of growth parameters, with the highest growth rate observed in the 20 mg kg-1 AFE group. In conclusion, dietary supplementation with 20 mg AFE kg-1 may be used as a growth promoter and immunostimulant in Nile tilapia aquaculture.

Multipopulational transcriptome analysis of post-weaned beef cattle at arrival further validates candidate biomarkers for predicting clinical bovine respiratory disease

Bovine respiratory disease (BRD) remains the leading infectious disease in post-weaned beef cattle. The objective of this investigation was to contrast the at-arrival blood transcriptomes from cattle derived from two distinct populations that developed BRD in the 28 days following arrival versus cattle that did not. Forty-eight blood samples from two populations were selected for mRNA sequencing based on even distribution of development (n = 24) or lack of (n = 24) clinical BRD within 28 days following arrival; cattle which developed BRD were further stratified into BRD severity cohorts based on frequency of antimicrobial treatment: treated once (treated_1) or treated twice or more and/or died (treated_2+). Sequenced reads (~ 50 M/sample, 150 bp paired-end) were aligned to the ARS-UCD1.2 bovine genome assembly. One hundred and thirty-two unique differentially expressed genes (DEGs) were identified between groups stratified by disease severity (healthy, n = 24; treated_1, n = 13; treated_2+, n = 11) with edgeR (FDR ≤ 0.05). Differentially expressed genes in treated_1 relative to both healthy and treated_2+ were predicted to increase neutrophil activation, cellular cornification/keratinization, and antimicrobial peptide production. Differentially expressed genes in treated_2+ relative to both healthy and treated_1 were predicted to increase alternative complement activation, decrease leukocyte activity, and increase nitric oxide production. Receiver operating characteristic (ROC) curves generated from expression data for six DEGs identified in our current and previous studies (MARCO, CFB, MCF2L, ALOX15, LOC100335828 (aka CD200R1), and SLC18A2) demonstrated good-to-excellent (AUC: 0.800–0.899; ≥ 0.900) predictability for classifying disease occurrence and severity. This investigation identifies candidate biomarkers and functional mechanisms in at arrival blood that predicted development and severity of BRD.

Modulatory effect of dietary copper nanoparticles and vitamin C supplementations on growth performance, hematological and immune parameters, oxidative status, histology, and disease resistance against Yersinia ruckeri in rainbow trout (Oncorhynchus mykiss).

Copper and vitamin C are micronutrients needed for the living organism's functions. Vitamin C has a great effect on the immune system of fish. The present study aimed to evaluate the effects of dietary copper nanoparticles (Cu-NPs) and vitamin C (VC) supplementations on rainbow trout (Oncorhynchus mykiss) juveniles. So, 216 rainbow trout juveniles were randomly assigned to six groups with trial diets supplemented with Cu-NPs and VC including 0/0 (T1, control diet), 0/250 (T2), 0/500 (T3), 2/250 (T4), 2/500 (T5), and 2/0 (T6) mg Cu-NPs/VC per kg diet. After the feeding trial for 60days, the fish were challenged with Yersinia ruckeri, and the survival rate was calculated for 15days. Based on the data analysis, weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER), lysozyme, alternative complement activity (ACH50), hematocrit (Hct), hemoglobin (Hb), and mean corpuscular volume (MCV) were significantly (p < 0.05) increased in the fish fed on T4 and T5 diets compared with the control group. Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) were significantly (p < 0.05) decreased in the fish fed with diets contain Cu-NPs and VC (T4 and T5). The expressions of TNF-α, IL-1ß, IL-10, SOD, CAT, and GPX genes were significantly (p < 0.05) decreased in the fish fed on T3, T4, and T5 diets versus the control. In addition, the dietary Cu-NPs and VC supplementations significantly enhanced resistance against pathogens and led to the control of infection in rainbow trout. In conclusion, Cu-NPs and VC administered as feed additives at 2/250-500mg/kg elevated the growth performance, antioxidant capacity, and health of rainbow trout.

The synergistic effects of plant polysaccharide and Pediococcus acidilactici as a synbiotic additive on growth, antioxidant status, immune response, and resistance of Nile tilapia (Oreochromis niloticus) against Aeromonas hydrophila

This study evaluated the growth performance, immune responses, and disease resistance of Nile tilapia upon pistachio hulls derived polysaccharide (PHDP) and Pediococcus acidilactici (PA) separately or as synbiotic. Fish received four types of diets: T1, control; T2, PHDP (0.1%); T3, PA (0.2%); T4, PHDP (0.1%) +PA (0.2%) for 56 days. The results showed that final weight and weight gain were markedly higher in fish fed T4 diet than that given T1 and T2 diets (P ≤ 0.05). In addition, a significantly greater specific growth rate was obtained by the T4 diet compared to the control. Fish survival was significantly improved in all supplemented diets compared to the control. On the other hand, the activities of lipase, protease, and amylase showed significant increases in the T4 group compared with other feeding groups. The total leucocytes and lymphocytes proportion significantly elevated in T3 and T4 than remaining groups (P ≤ 0.05). Further, fish fed T3 diet presented significantly higher serum total protein, total immunoglobulin, lysozyme activity (LYZ), alternative complement activity (ACH50), and alkaline phosphatase activity compared to fish fed T1 and T2 diets, while the mentioned indices were found significantly highest in T4 group than others. Fish received T3 and T4 diets had higher skin mucus LYZ and ACH50 than those fed T1 and T2 diets (P ≤ 0.05). The malondialdehyde levels were significantly declined in T3 and T4 when compared to the control. Fish fed T3 and T4 diets demonstrated significantly enhanced superoxide dismutase, catalase, and glutathione peroxidase activities compared to the control. The intestinal propionic acid significantly increased by T2 and T4 diets, while the highest levels of acetic acid detected in fish given T4 diet. The expression levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 10 (IL-10) were significantly affected by T3 and T4 supplements. The efficacy of T4 diet against Aeromonas hydrophila infection was documented by a significantly lower mortality rate. In conclusion, the combination of PHDP and PA presented promising results as a synbiotic feed additive for Nile tilapia.

Remarkable positive effects of figwort (Scrophularia striata) on improving growth performance, and immunohematological parameters of fish

This study was conducted to investigate the effect of figwort on the growth and immunohematological parameters of common carp (14.20 ± 0.53 g). Four experimental diets were developed to feed fish for eight weeks: control, Figw10 (10 g/kg figwort), Figw20 (20 g/kg figwort), and Figw30 (30 g/kg figwort). The results showed that fish fed dietary Figw10 gained more weight (38.25 g) than control (P < 0.05). Regarding immunohematological parameters, fish fed dietary Figw30 had a higher level of white blood cells (31.2 103/mm3), hematocrit (35.82%), blood performance (14.63), total protein (1.96 g/dL), albumin (0.79 g/dL), globulin (1.17 g/dL), lymphocyte (70.53%), monocyte (3.03%), alternative hemolytic complement activity (ACH50) (147.76 u/mL), lysozyme (62.19 u/mL), and bactericidal activities (135.24) than the control group (P < 0.05). After 14 days of the challenge with Aeromonas hydrophila, the Figw30 treatment had the highest survival ratio (61.76%) compared to the control with 26.46%. Further, after the challenge, fish fed dietary Figw30 had a higher value of immunoglobulin M (42.00 μg/mL), antibody titer (19.23), complement component 3 (296.39 μg/mL), and complement component 4 (97.91 μg/mL) when compared with those fed control diet (P < 0.05). In conclusion, the optimum dosage for providing the best immune response was 30 g/kg in diet.

The effects of combined inclusion of Malvae sylvestris, Origanum vulgare, and Allium hirtifolium boiss for common carp (Cyprinus carpio) diet: Growth performance, antioxidant defense, and immunological parameters

The present study aimed to investigate the effects of a mixture of three medicinal plants extracts (COP: common mallow (Malvae sylvestris), oregano (Origanum vulgare), and Persian shallot (Allium hirtifolium boiss)) on growth, hematological indices, immunological parameters, liver antioxidant, and digestive enzyme activity of common carp (Cyprinus carpio). Accordingly, 540 common carp fingerlings were randomly allotted to 18 fiberglass tanks, including six treatments each in triplicate. Fish were fed with experimental diets supplemented with 0, 0.5, 1, 2, 3, and 5% of the herbal mixture. After 60 days, the effects on growth performance, antioxidant, and immunological parameters were evaluated. According to the results, the highest final weight was observed in the fish fed 2 and 3% of the herbal mixture. Also, the feed conversion ratio (FCR) showed a significant decrease in fish treated with the herbal mix, so that the lowest FCR was observed in the treatment 1%. Hematological examinations such as red blood cells (RBC), white blood cell (WBC), and hemoglobin showed significant changes between different parameters compared to the control group. The highest protein content was observed in the fish supplemented with 2, 3, and 5% herbs. Besides, in contrast to glucose, the cortisol level showed a significant decrease compared to the control group. The digestive enzymes (Amylase, Lipase, and Protease) were significantly higher in 2 and 3% treatments than in the control group. Also, a significant difference was found in Superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and malondialdehyde (MDA) content between the experimental and control treatments. Examination of liver enzymes (and alanine aminotransaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)) showed a significant difference in herbal mixture treatments with the control group, according to which the lowest amount of these enzymes was recorded in 2 and 3% herb supplemented fish. Herbal mix resulted in higher mucosal and intestinal immunity parameters, including total immunoglobulin (total Ig), lysozyme, alternative complement activities (ACH50), protease, and ALP. According to the results, supplementing the diet with a mixture of the COP can significantly improve growth parameters, stimulate the innate immune system, and improve antioxidant defenses and liver health of common carp.

Complement Activation Is a Prominent Feature of MOGAD.

Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated diseases (MOGADs) account for a substantial proportion of pediatric and adult patients who present with acquired demyelinating disorders. Its pathogenesis and optimal therapy are incompletely understood. We profiled systemic complement activation in adult and pediatric patients with MOGAD compared with patients with relapse-onset multiple sclerosis, patients with neuromyelitis optica spectrum disorder, and pediatric control and adult healthy donors. Proteins indicative of systemic classical and alternative complement activation were substantially increased in patients with MOGAD compared to control groups. Elevated levels were detected in both adult and pediatric cases and across all clinical syndromes. Complement inhibition should be explored for its therapeutic merit in patients with MOGAD. ANN NEUROL 2021;90:976-982.

Dietary supplementation with powder and gelatine micro and nanoencapsulated sodium propionate: Influence on growth performance, digestive and antioxidant enzymes and mucosal immunity of koi carp ( Cyprinus carpio koi)

The current study evaluated the efficiency of three forms of dietary sodium propionate (SP) on growth performance, digestive and liver antioxidant enzymes activities, as well as skin mucus immune responses of koi carp (Cyprinus carpio koi) fingerlings. Gelatine micro and nanoparticles loaded with SP were synthetized and expressed as gelatine-SP MPs and gelatine-SP NPs, respectively. Basal diet was supplemented with gelatine microparticles, gelatine nanoparticles, powder-SP, gelatine-SP MPs and gelatine-SP NPs. Fish were distributed into 18 experimental units and fed with prepared diets for eight weeks. The results indicated that the growth performance improved in fish fed SP-supplemented diets in comparison with the controls. The highest growth performance was observed in gelatine-SP NPs followed by gelatine-SP MPs. The digestive enzymes activity including protease, trypsin, lipase and α-amylase in gelatine-encapsulated SP micro and nanoparticles dietary groups increased significantly in comparison with other dietary groups (p < .05). The use of SP-loaded micro and nanoparticles decreased the liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in comparison to other groups (p < .05). Feeding fish with SP-supplemented diets led to increasing antioxidant enzymes of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), as well as alkaline phosphatase (ALP) in the liver tissue in comparison to the controls (p < .05). The skin mucus lysozyme, alternative haemolytic complement activity (ACH50) and total immunoglobulin (Ig) levels were higher in SP-dietary groups than the controls; the highest levels were in gelatine-SP NPs dietary group (p < .05). The findings confirmed that the administration of SP loaded into micro and nanoparticles of gelatine could improve its efficiency in the diet of koi fish.

Effect of Leucas aspera Against Aeromonas hydrophila in Nile Tilapia (Oreochromis niloticus): Immunity and Gene Expression Evaluation

The present study addressed the effects of Leucas aspera enriched diet in Nile tilapia. Three hundred Nile tilapia were fed Leucas aspera as follows: 0 g kg-1 L. aspera (C-control), 5 g kg-1 L. aspera (T1), 10 g kg-1 L. aspera (T2) and 15 g kg-1 L. aspera (T3). After 30 days of feeding, significant (P&lt;0.05) increase in growth performance was noticed by feeding the fish the T2 diet. Thereafter fish were intraperitoneal injected with Aeromonas hydrophila in challenge test. After 21 days of challenge, highest survival rate (70%) was observed in fish fed the T3 diet followed by fish fed T2 diet (65%). Serum immunological parameters such as phagocytosis, alternative complement activity, respiratory burst activity and lysozyme activity were significantly (P&lt;0.05) enhanced in fish fed all inclusion levels of L. aspera with the maximum activity in fish fed the T2 diet. Hematological parameters were significantly (P&lt;0.05) higher in all groups fed L. aspera diets vs. control fed fish. No histopathological changes in liver were observed in fish fed the T2 diet in the histology study. Gene expression study revealed the upregulation in the expression of COX-2 and GR genes. In conclusion, the current results suggest that dietary administration of L. aspera especially the T2 diet, has beneficial effects in improving immunity and can mitigate the adverse effects of A. hydrophila infection in Nile tilapia.

Effects of dietary vitamin E on growth performance, body composition, antioxidant capacity, and some immune responses in Caspian trout (Salmo caspius)

This study was conducted to evaluate the effect of dietary vitamin E on growth performance, feed utilization, biochemical properties and some immune responses in Caspian trout, Salmo caspius. Six experimental diets were formulated with semi-purified ingredients supplemented with vitamin E in the form of DL-α-tocopherol acetate to provide the actual vitamin E concentrations of 4.9 (the basal diet), 8.6, 17.4, 35.4, 78.8 and 137.0 mg kg−1 diet, respectively. Each diet was assigned to three replicate groups of Caspian trout (initial average weight of 9.73 ± 0.34 g) for eight weeks. Weight gain ratio (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) were found to be significantly enhanced by increasing dietary vitamin E level and reached to the highest values in fish fed with 78.8 mg kg−1 vitamin E supplemented diet (P < 0.05). A significantly linear increasing trend was recorded in crude protein, fat content, superoxide dismutase (SOD) activity, liver vitamin E concentration, immunoglobulin M (IgM), and alternative complement activity (ACH50), while glutathione peroxidase (GPX) activity was linearly and quadratically enhanced in response to increasing dietary vitamin E supplementations (P < 0.05). There were also linearly and quadratically decreasing trend in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities as well as serum glucose (GLC) and malondialdehyde (MDA) levels by supplementing dietary vitamin E (P < 0.05). Analysis by the polynomial regression of SGR, GLC, and SOD activity against varying levels of dietary vitamin E revealed that the optimum dietary vitamin E requirements in Caspian trout were 79.44, 78.73, and 82.16 mg kg−1, respectively.

Low molecular weight polysialic acid prevents lipopolysaccharide-induced inflammatory dopaminergic neurodegeneration in humanized SIGLEC11 transgenic mice.

Parkinson's disease is one of the most common neurodegenerative diseases in the elderly population, with a pathophysiology linked to neuroinflammation, complement activation, and oxidative damage. Soluble polysialic acid with an average degree of polymerization 20 (polySia avDP20) prevents inflammation and oxidative burst in human macrophages via sialic acid-binding immunoglobulin like lectin-11 (SIGLEC11) receptor and interferes with alternative complement activation. Here, we confirmed the anti-inflammatory capacity of polySia avDP20 on cultured murine embryonic stem cell-derived microglia and analyzed the effect of polySia avDP20 in a lipopolysaccharide-triggered animal model of Parkinson's disease. We demonstrated a neuroprotective effect of intraperitoneally applied polySia avDP20 in humanized SIGLEC11 transgenic mice after repeated systemic challenge with lipopolysaccharide. Pathway enrichment analysis of the brain transcriptome on day 19 after disease initiation showed that intraperitoneal application of 10μg/g body weight polySia avDP20 prevented excessive inflammation. In line with these data, polySia avDP20 attenuated the lipopolysaccharide-triggered increase in mRNA levels of immune-related genes (Il1b, Cd14, Myd88, Fcer1g, Itgam, C4, Cybb, Iba1 and Cd68) and cell death-related genes (Casp8, Ripk1 and Ripk3) in the brains of SIGLEC11 transgenic mice on day 19, but not on day 5. Moreover, immunohistochemistry demonstrated that polySia avDP20 reduced the lipopolysaccharide-induced increase in immunoreactivity of IBA1 and CD68 in the substantia nigra pars reticulata in SIGLEC11 transgenic and wild type mice on day 19. Furthermore, treatment with polySia avDP20 prevented the loss of dopaminergic neurons in the substantia nigra pars compacta induced by lipopolysaccharide challenge in both SIGLEC11 transgenic and wild type mice on day 19. Thus, our data demonstrate that polySia avDP20 ameliorates inflammatory dopaminergic neurodegeneration and therefore is a promising drug candidate to prevent Parkinson's disease-related inflammation and neurodegeneration.

The effect of dietary combined herbs extracts (oak acorn, coriander, and common mallow) on growth, digestive enzymes, antioxidant and immune response, and resistance against Aeromonas hydrophila infection in common carp, Cyprinus carpio

The objective of the present investigation was to evaluate the effects of the combination of medicinal herbs extracts (CMO: Coriander (Coriandrum sativum), common mallow (Malva sylvestris), and oak acorn (Quercus brantii)) on growth, digestive enzymes activity, immune parameters, and disease resistance in common carp, Cyprinus carpio. A total number of three hundred fish (20.80 ± 0.25 g) were randomly attributed to five treatments fed with diets containing 0 (control), 0.5%, 1%, 3%, and 5% of CMO for a period of 60 days then were challenged with A. hydrophila infection. Based on the results, there were significant differences in all growth parameters, including final weight (FW), weight gain (WG), specific growth rate (SGR), and food conversion ratio (FCR) between CMO supplemented fish and control with the maximum values in the 5% CMO treatment (P < 0.05). Despite the control fish, no mortality was observed in CMO treatments (P < 0.05). CMO diets increased red blood cells (RBC), white blood cells (WBC), hematocrit (Hct), hemoglobin (HB), and mean corpuscular volume (MCV), while decreased mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). Feeding the fish with CMO diets markedly increased total protein, albumin, and globulin values, while triglyceride, cholesterol, glucose, and cortisol decreased (P < 0.05). Antioxidant biomarkers in CMO-fed fish were significantly higher than those of the control group. Immune parameters in serum and mucus including lysozyme, total immunoglobulin (Total Ig), nitroblue tetrazolium (NBT), alternative complement activity (ACH50), protease, alkaline phosphatase (ALP), and antioxidant enzymes were significantly higher in CMO-fed fish compared to the control group (P < 0.05). The highest and the lowest survival rates following a challenge with A. hydrophila were observed in 3% CMO and the control treatments, respectively. Polynomial regression analysis showed that the the best recommended inclusion level of CMO was 1% to maximize growth performance and improved feed conversion values. In conclusion, our findings revealed that the 3% CMO could elevate the growth, immune systems, antioxidant activity, and resistance to A. hydrophila in common carp.

Effect of different dietary arachidonic, eicosapentaenoic, and docosahexaenoic acid content on selected immune parameters in gilthead sea bream (Sparus aurata)

The increasing replacement of fish oil (FO) by vegetable oils (VO) in aquafeeds for marine carnivorous species may lead to modifications of the dietary arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) levels and ratios that may compromise the fish immune status. Therefore, this study aimed to assess how different dietary ratios of ARA, EPA, and DHA modulate the immune response of gilthead sea bream juveniles. For that purpose, four isoproteic and isolipidic plant-based diets were formulated to include different dietary Long-Chain-Polyunsaturated Fatty Acids (LC-PUFA) ratios (%DM): Diet A (2.0% ARA: 0.2% EPA: 0.1% DHA); Diet B (1.0% ARA: 0.4% EPA: 0.4% DHA); Diet C (0% ARA: 0.6% EPA: 0.6% DHA); Diet D (0% ARA: 0.3% EPA: 1.5% DHA). Fish were fed the experimental diets for 56 days and then the haematological profile, humoral innate immune parameters, and expression of immune-related genes in the gut were determined. Our results showed that fish fed diet B exhibited an increase in the monocyte numbers, alternative complement activity, and bactericidal activity against Photobacterium damselae compared to the values found in fish fed other diets. Contrarily, peroxidase, antiproteases, and proteases activity and nitric oxide levels were not affected by the dietary treatments. Immune-related gene expression in the distal intestine did not show differences between dietary treatments. Overall, a diet with a balanced n-6 (ARA) and n-3 (EPA+DHA) LC-PUFA ratio seemed to better modulate the fish innate immune response, thus better preparing the fish innate immune system against potential immunological insults.