Combined immune score predicts the prognosis of newly diagnosed multiple myeloma patients in the bortezomib-based therapy era.

ABSTRACT: To investigate the effect of a combined immune score including the lymphocyte-to-monocyte ratio (LMR) and uninvolved immunoglobulin (u-Ig) levels on the prognosis of newly diagnosed multiple myeloma (NDMM) patients treated with bortezomib.Clinical data of 201 NDMM patients were retrospectively analyzed. Patients with LMR ≥ 3.6 and LMR < 3.6 were scored 0 and 1, respectively. Patients with preserved u-Ig levels, suppression of 1 u-Ig, and suppression of at least 2 u-Igs were scored 0, 1, and 2, respectively. The immune score, established from these individual scores, was used to separate patients into good (0-1 points), intermediate (2 points), and poor (3 points) risk groups. The baseline data, objective remission rate (ORR), whether receive maintenance treatment regularly and overall survival of patients before treatment were analyzed.The ORR of the good-risk group was significantly higher than that of the intermediate-risk group (75.6% vs 57.7%, P = .044) and the poor-risk group (75.6% vs 48.2%, P = .007). The multivariate analysis results showed that age ≥ 65 years, International Staging System stage III, platelet count ≤ 100 × 109/L, lactate dehydrogenase (LDH) > 250 U/L, serum calcium > 2.75 mmol/L, no receipt of regular maintenance treatment, LMR < 3.6, suppressed u-Igs = 1, suppressed u-Igs ≥ 2, intermediate-risk group and poor-risk group were independent predictors of poor overall survival.In the bortezomib era, the LMR, u-Ig levels, and the immune score play an important role in the prognosis of NDMM patients. Among them, the immune score showed the strongest prognostic value, and it could be a beneficial supplement for the early identification of high-risk patients.

Interaction between the level of immunoglobulins and number of somatic cells as a factor shaping the immunomodulating properties of colostrum.

The aim of this study was to investigate the association between immunoglobulins and SCC as a factor in shaping the content of the immunostimulatory components of colostrum. Seventy-eight multiparous Polish Holstein-Friesian cows were selected for the experiment. Colostrum samples were collected immediately after calving (up to a max. of 2 h). The cows were divided into groups according to the following levels: Immunoglobulins (IG class)-(IG1) over 50 g/L, (IG2) up to 50 g/L; SCC class-(SCC1) up to 400 000/ml, (SCC2) 400-800 000/ml, (SCC3) over 800 000/ml. Colostrum assigned to the IG1 SCC1 group had a statistically significant higher (p ≤ 0.01) concentration of both whey proteins and fatty acids compared to the IG1 SCC2 and SCC3 groups. The concentration of IgG, IgM, and IgA was shown to be higher in IG1 SCC1 than IG2 SCC3 by 226%, 149%, and 115%, respectively. The concentration of lactoferrin was shown to be higher in IG1 SCC1 than IG2 SCC3 by 149%. The determination of colostrum quality based on the concentration of immunoglobulins in the colostrum may not be sufficient because serum IgG concentrations at birth show a linear increase relative to colostrum SCC. A breakdown of colostrum into quality classes, taking into account the level of SCC, should therefore be introduced.

Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy.

INTRODUCTION: There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). OBJECTIVE: We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. METHODS: Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. RESULTS: At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P < .01). TGP-IgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P < .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response. CONCLUSIONS: The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differences in the mechanisms of action.

Supplementation of antioxidant micronutrients reduces stress and improves immune function/response in periparturient dairy cows and their calves.

BACKGROUND: Periparturient period induces stress in cows which fluctuates hormonal and metabolic function and causes immune suppression. Apart from impairing the health, production, and reproduction of cows, it also influences the well-being of newborn calves by decreasing the colostrum quality. Micronutrients are known for optimal health and production and their effects on parturition stress, immune response in both cow and its calf need to be explored. AIM: The aim of this study was to see the effect of oral supplementation of micronutrients during the prepartum period on the health status of crossbred dairy cows and subsequently on their newborn calves. METHODS: A total of 42 healthy multiparous cows were selected and randomly divided into five groups with seven cows in each group, i.e. control (Basal Diet, BD), VA group (BD + vitamin A, 105 IU), Zn group (BD + zinc sulphate, 60 ppm), VE group (BD + vitamin E, 2500 IU), and combined supplementation (CS) group (BD + combination of VA, Zn, and VE). The supplements were offered in compounded concentrate DM (100 g) to individual cows once daily before the morning feeding and the remaining portion was incorporated in the TMR. Feeding was started one month before the expected days of calving till calving. Blood samples were collected from cows at days -15, -7, -3, 0, +3, +7, and +15 relative to the day of calving. Blood samples from newborn calves and milk samples of cows were collected at days 0, +3, +7, and +15. Milk somatic cell counts (SCC) were estimated using a cell counter. Cortisol was estimated by ELISA kit in blood and milk plasma of cows and in the blood plasma of their calves. Total immunoglobulins (Ig) were estimated in milk of cows and serum of calves using zinc sulphate turbidity method. Blood neutrophils from cows and calves were studied for phagocytic activity (PA) using nitro blue tetrazolium (NBT) assay.Data were analysed by repeated-measures two-way ANOVA using the mixed procedure of SAS, and the pairwise comparison was performed using a multiple comparison test (Tukey). RESULTS: Combined supplementation of micronutrients decreased (P < 0.05) maternal blood plasma (control vs. CS group, 5.98 ±â€¯0.20 vs. 3.86 ±â€¯0.23 ng/mL) and milk plasma (3.96 ±â€¯0.13 vs. 2.71 ±â€¯0.10 ng/mL) cortisol, milk SCC (3.05 ±â€¯0.11 vs. 2.12 ±â€¯0.10 × 105 cells/mL) and increased (P < 0.05) total milk Ig concentration (18.80 ±â€¯0.11 vs. 23.04 ±â€¯0.57 mg/mL) and the PA of blood neutrophils (0.84 ±â€¯0.03 vs. 1.07 ±â€¯0.03). Similarly, lower blood cortisol concentration (9.69 ±â€¯0.35 vs. 6.02 ±â€¯0.18 ng/mL) and higher (P < 0.05) total Ig (23.26 ±â€¯0.11 vs. 30.34 ±â€¯0.70 mg/mL) and PA of blood neutrophils (0.37 ±â€¯0.02 vs. 0.52 ±â€¯0.02) were observed in the calves born to CS group of cows as compared to the control. Highest (P < 0.05) positive effects (lower stress levels and higher immune response) of treatment were noticed in CS group followed by VE group and then Zn group. However, VA group didn't differ from the control group. CONCLUSION: Our results indicate that micronutrient interventions during the prepartum period can improve the health status of dairy calves and subsequently the well-being of their calves.

Impact of intraoperative allogenic and autologous transfusion on immune function and prognosis in patients with hepatocellular carcinoma.

The effect of intraoperative blood transfusion on the immune function and prognosis of hepatocellular carcinoma (HCC) has not been fully investigated. The aim of this study was to evaluate the effects of intraoperative autologous blood transfusion and allogeneic blood transfusion on immune function and prognosis in surgically treated HCC patients. One hundred fourteen primary hepatic carcinoma patients who would undergo selective operations were divided into two groups, 35 patients in the experimental group received intraoperative autologous blood transfusion and 79 patients in the control group received allogeneic blood transfusion. The amount of serum T lymphocyte subsets, natural killer (NK) cells and immunoglobulin before and after operation, as well as the recurrence-free survival (RFS) were compared. Results shown that, there was no significant difference in the level of immunocytes and immunoglobulin between the two groups before treatment (P > .05). At 1 day after surgery, there were significant differences in T lymphocyte, NK cells and immunoglobulin levels before and after transfusion. CD3+, CD4+, CD4+/CD8+, and NK cells in autologous transfusion group were significantly higher than those in allogeneic transfusion group (P < .05); the level of IgG, IgM, and IgA in allogeneic transfusion group were significantly lower than those before operation (P < .05), the level of IgG, IgM, and IgA in autologous transfusion group did not significantly fluctuate, and significantly higher than those of allogeneic transfusion group (P < .05). At 5 days after surgery, all indexes of autologous transfusion group recovered to the preoperative level, the levels of CD3+, CD4+, CD4+/CD8+, NK cells, IgG, IgM, and IgA were significantly higher than those of allogeneic transfusion group (P < .05). The follow-up results showed that the RFS of autologous transfusion group was significantly higher than that of allogeneic transfusion group (P < .05). In conclusion, compared with allogeneic blood transfusion, intraoperative autologous blood transfusion possessed less impact on immune function, it may even improve immune function and RFS in HCC patients after surgery. Therefore, HCC patients should be recommended to receive autologous blood transfusion instead of allogeneic blood transfusion when they need blood transfusion during the perioperative period.

Consequences of Vitamin A Deficiency: Immunoglobulin Dysregulation, Squamous Cell Metaplasia, Infectious Disease, and Death.

Vitamin A is an important regulator of immune protection, but it is often overlooked in studies of infectious disease. Vitamin A binds an array of nuclear receptors (e.g., retinoic acid receptor, peroxisome proliferator-activated receptor, retinoid X receptor) and influences the barrier and immune cells responsible for pathogen control. Children and adults in developed and developing countries are often vitamin A-deficient or insufficient, characteristics associated with poor health outcomes. To gain a better understanding of the protective mechanisms influenced by vitamin A, we examined immune factors and epithelial barriers in vitamin A deficient (VAD) mice, vitamin D deficient (VDD) mice, double deficient (VAD+VDD) mice, and mice on a vitamin-replete diet (controls). Some mice received insults, including intraperitoneal injections with complete and incomplete Freund's adjuvant (emulsified with PBS alone or with DNA + Fus-1 peptide) or intranasal inoculations with Sendai virus (SeV). Both before and after insults, the VAD and VAD+VDD mice exhibited abnormal serum immunoglobulin isotypes (e.g., elevated IgG2b levels, particularly in males) and cytokine/chemokine patterns (e.g., elevated eotaxin). Even without insult, when the VAD and VAD+VDD mice reached 3-6 months of age, they frequently exhibited opportunistic ascending bacterial urinary tract infections. There were high frequencies of nephropathy (squamous cell hyperplasia of the renal urothelium, renal scarring, and ascending pyelonephritis) and death in the VAD and VAD+VDD mice. When younger VAD mice were infected with SeV, the predominant lesion was squamous cell metaplasia of respiratory epithelium in lungs and bronchioles. Results highlight a critical role for vitamin A in the maintenance of healthy immune responses, epithelial cell integrity, and pathogen control.

Maternal Immunoglobulins in Infants-Are They More Than Just a Form of Passive Immunity?

In the present review, we highlight the possible "extra-immunological" effects of maternal immunoglobulins (Ig) transferred to the blood circulation of offspring, either via the placenta before birth or via the colostrum/milk across the gut after birth in different mammalian species. Using the newborn pig as a model, since they are naturally born agammaglobulinemic, intravenously (i.v.) infused purified serum Ig rapidly improved the vitality, suckling behavior, and ensured the survival of both preterm and term piglets. In further studies, we found that proper brain development requires i.v. Ig supplementation. Studies have reported on the positive effects of i.v. Ig treatment in children with epilepsy. Moreover, feeding newborn pigs an elementary diet supplemented with Ig improved the gut structure, and recently a positive impact of enteral or parenteral Ig supplementation on the absorption of polyunsaturated fatty acids (PUFAs) was observed in the newborn pig. Summarized, our own results and those found in the literature, indicate the existence of important extra-immune effects of maternal Ig, in addition to the classical protective effects of transferred maternal passive immunity, including effects on the development of the brain, gut, and possibly other organ systems in the neonate. These additional properties of circulating Ig could have an impact on care guidelines for human neonates, especially those born prematurely with low plasma Ig levels.

The effect of capsulated and noncapsulated egg-yolk-specific antibody to reduce colonization in the intestine of Salmonella enterica ssp. enterica serovar Infantis-challenged broiler chickens.

The antibacterial properties of egg yolk antibodies have been known for many years. Enhanced antibiotic resistance has resulted in increased need for using these antibodies as an alternative. In the present study, generation, capsulation, and inhibition growth properties of IgY directed against Salmonella enterica subsp. enterica serovar Infantis (SI) were evaluated. White Leghorn layer hens were immunized using whole cell of inactivated SI. Salmonella Infantis-specific antibody activities in sera and egg yolk were determined by ELISA. A total of 480 one-day-old male "Cobb 500" chicks were randomly divided into 8 groups, with 6 replications of 10 birds kept for 21 D. All birds from 7 challenged groups were orally inoculated with 1 mL of SI suspension (1 × 107 CFU/mL) at 3 and 4 D of age. Two groups were dietary supplemented with 5 g/kg immune powdered yolk or nonimmune powdered yolk. One group was dietary supplemented with 12.8 g/kg capsulated immune yolk (CIY). Two groups were given 8.3 mL/L of immune water-soluble yolk or nonimmune water-soluble yolk fraction in drinking water. In the antibiotic group, 1 mL/L Enrofloxacin 10% was added to drinking water. All supplements except for the antibiotic (on Day 4 for 10 D) were added on day one and continued during the experiment. Negative and positive control groups received no supplements. During the experiment, among the challenged groups, the minimum SI cecal colonization and the lowest isolation of SI from the liver (P < 0.01) was observed in the antibiotic group. Following antibiotic group, in the group receiving CIY, colonization of bacteria in ceca and liver was significantly reduced during the second and third weeks of the experiment (P < 0.01). According to the results, capsulated specific IgY has a beneficial effect in reducing the colonization of Salmonella under the conditions of this study in comparison with other forms of IgY antibody.

The Yin and Yang of RNA surveillance in B lymphocytes and antibody-secreting plasma cells.

The random V(D)J recombination process ensures the diversity of the primary immunoglobulin (Ig) repertoire. In two thirds of cases, imprecise recombination between variable (V), diversity (D), and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbour biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, focusing on the benefits of nonsense- mediated mRNA decay (NMD) activation during B-cell development and detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells. [BMB Reports 2019; 52(12): 671-678].

Transfer of passive immunity in dairy calves: the effectiveness of providing a supplementary colostrum meal in addition to nursing from the dam.

Failed transfer of passive immunity (FTPI) in dairy calves - which is often due to the low amount of colostrum provided within a few hours after birth - remains a crucial issue. Enabling dairy calves to nurse colostrum from their dams could be useful in increasing intake and thus avoiding FTPI, but further potential effects on the health and welfare of both calves and dams should also be considered. In this study, 107 calf-dam pairs from two Italian dairy farms were alternately assigned to one of the following colostrum provision methods (CPMs): 'hand-fed method' (HFM) - the calf was separated from the dam immediately after birth and colostrum was provided by nipple-bottle (n = 50); 'nursing method' (NM) - the calf nursed colostrum from the dam for the first 12 h of life without farmer assistance (n = 30); and 'mixed method' (MM) - the nursing calf received a supplementary colostrum meal by nipple-bottle (n = 27). Serum of calves (1 to 5 days of age) and samples of their first colostrum meal were analysed by electrophoresis to assess immunoglobulin (Ig) concentration. Additionally, behavioural indicators of separation distress (calf and dam vocalisations; calf refusal of the first meal after separation; undesirable dam behaviour at milking) in the following 24 h were recorded as binary variables (Yes/No), and the health status of calves (disease occurrence and mortality) and dams (postpartum disorders and mastitis occurrence) were monitored for the first 3 months of life and 7 days after parturition, respectively. The lowest FTPI occurrence (calf serum Ig concentration <10.0 g/l) was found in the MM (11.1%) and the HFM (22.0%) compared with the NM (60.0%) (P<0.05), and the highest percentage of calves with optimal transfer of passive immunity (serum Ig concentration ≥16.0 g/l) was observed in the MM (55.6%). The lowest calf-dam separation distress was observed in the HFM (P<0.05). The highest calf disease occurrence was recorded in the HFM (64.0%) and the lowest in the NM (33.3%), with an intermediate value for the MM (44.4%) (P<0.05). No effect of the CPM was observed on dam health or calf mortality (P>0.05). The results of this study indicated that providing calves with a supplementary colostrum meal in addition to nursing from the dam (MM) is truly effective in maximizing passive immunity transfer. Anyway, specific strategies should be studied to minimise calf-dam separation distress.

Anti-PirA-like toxin immunoglobulin (IgY) in feeds passively immunizes shrimp against acute hepatopancreatic necrosis disease.

Acute hepatopancreatic necrosis disease (AHPND), caused by a toxin-producing Vibrio parahaemolyticus strain, has become a serious threat to shrimp aquaculture. The need to regulate antibiotic use prompted the development of alternative ways to treat infections in aquaculture including the use of chicken egg yolk immunoglobulin (IgY) for passive immunization. This study evaluated the protective effect of IgY against AHPND infection in Litopenaeus vannamei (Boone). IgY was isolated from eggs laid by hens immunized with recombinant PirA-like (rPirA) and PirB-like (rPirB) toxins. Whole-egg powders having IgY specific to rPirA (anti-PirA-IgY) and rPirB (anti-PirB-IgY) and IgY from non-immunized hen (control-IgY) were mixed with basal diets at 20% concentrations and used to prefeed shrimp 3 days before the bacterial challenge test. Survival rates of the challenged shrimp fed the anti-PirA-IgY, anti-PirB-IgY and control-IgY diets were 86%, 14% and 0%, respectively. Only the feed containing anti-PirA-IgY protected shrimp against AHPND. Increasing the concentration of rPirA antigen to immunize hens and lowering the amount of egg powder in feeds to 10% consistently showed higher survival rates in shrimp fed with anti-PirA-IgY (87%) compared with the control (12%). These results confirm that addition of anti-PirA-IgY in feeds could be an effective prophylactic method against AHPND infection in shrimp.

In vitro efficacy of potentiated egg yolk powder against Campylobacter jejuni does not correlate with in vitro efficacy.

Campylobacter jejuni is a zoonotic agent responsible for the foodborne gastroenteritis campylobacteriosis. Control of C. jejuni load in the poultry primary production is recognized as an avenue to reduce human exposure to the pathogen. As for now, no commercially applicable control methods exist at the farm. Several studies tested egg yolk powders, potentiated or not against C. jejuni, as feed additives for chicken and suggested that the quantity and quality of the antibodies presence in the yolk are determinant factors for the full success of this approach. Unfortunately, data from these studies inconsistently showed a reduction of cecal C. jejuni carriage. Our first goal wwas to characterize (quantification by ELISA, agglutination test, bacterial antigen recognition profiles by Western blot, bactericidal effect by serum killing assays and C. jejuni mobility by soft agar migation) the antibodies extracted from egg yolk powders originating from different egg production protocols. Secondly, these powders were microencapsulated and recharacterized. Finally the protected powders were tested as a feed additive to destabilize C. jejuni colonization in an in vivo assay. Despite the in vitro results indicating the ability of the egg yolk powders to recognize Campylobacter and potentially alter its colonization of the chicken caecum, these results were not confirmed in the in vivo trial despite that specific caecal IgY directed toward Campylobacter were detected in the groups receiving the protected powders. More research is needed on Campylobacter in order to effectively control this pathogen at the farm.

Effect of IgY on Periodontitis and Halitosis Induced by Fusobacterium nucleatum.

Fusobacterium nucleatum is a morbific agent in periodontitis and halitosis. Egg yolk antibody (IgY) was obtained from egg yolks from chickens stimulated with F. nucleatum. This study was to assess the effectiveness of IgY on periodontitis and halitosis caused by F. nucleatum in vitro and in vivo. The growth of F. nucleatum was inhibited (p <0. 05) by different concentrations of IgY in vitro and the results of a Halimeter show volatile sulfur compounds (VSCs) were reduced to 904 ± 57 ppb at a concentration 40 mg/ml of IgY. The changes of fatty acids of F. nucleatum were determined using GC-MS. The scores for odor index of rat saliva were decreased. The major constituent of volatile organic compounds (VOCs) including short-chain acids decreased 46.2% in 10 mg/ml IgY, ammonia decreased 70% in 40 mg/ml IgY, while aldehydes and olefine ketones were almost unchanged. The ELISA assay revealed that IL-6 and TNF-α were decreased after 4 weeks' IgY treatment. Morphometric (X-ray) and histological analyses (HE) showed that IgY reduced alveolar bone loss and collagen fibers became orderly in rat models. As a result, IgY may have the potential to treat periodontitis and halitosis.

Targeting Endothelial Ligands: ICAM-1/alicaforsen, MAdCAM-1.

Specific blockade of the endothelial ligands intercellular adhesion molecule-1 [ICAM-1] and mucosal addressin cell adhesion molecule [MAdCAM] involved in leukocyte recruitment to the site of inflammation as therapeutic targets in inflammatory bowel disease [IBD] has been recognized from their overexpression in the inflamed mucosa and successful intervention based on these ligands in preclinical animal models. Interventions to target ICAM-1 in human IBD are confined to the ICAM-1 anti-sense oligonucleotide alicaforsen. While results with parenteral formulations of alicaforsen in Crohn's disease have largely been negative, efficacy signals derived from studies with an enema formulation in ulcerative colitis and pouchitis are promising and have led to a Food and Drug Administration Fast-Track designation for the latter. A large phase III programme in pouchitis is underway. Phase II studies with the anti-MAdCAM-1 antibody [SHP647] delivered positive results in ulcerative colitis and anti-inflammatory signals in Crohn's disease. Furthermore, it was shown that SHP647 does not affect the number and composition of cells in cerebrospinal fluid, suggesting that the compound is not affecting immune surveillance in the central nervous system. In addition, both alicaforsen and SHP647 are promising compounds based on the clear safety profile observed so far.

Physicochemical properties of anti Vibrio harveyi egg yolk antibody (IgY) and its immunological influence in Indian white shrimp Fenneropenaeus indicus.

Edible antibodies specific to host pathogens is an attractive approach to establish protective immunity, especially against gastrointestinal pathogens both in humans and animals. The edible antibody of anti-Vibrio harveyi IgY (anti-V. h IgY) was produced by antigen mixed with immunoadjuvant Asparagus racemosus and Glycine max. Hens were immunized and eggs were collected five weeks after the immunization. Anti-V. harveyi IgY stability in different digestive enzymes such as trypsin and chymotrypsin were evaluated to determine its ability to withstand in the gastrointestinal tract of F. indicus. Specific binding activity and concentration (average 9.5% of total IgY content) of the anti-V. h IgY were determined by the ELISA using V. harveyi antigen. Further the anti-V. h IgY diets including V.h wo, V.h A, V.h G and control diets were fed to F. indicus for 60 days. After 30 and 60 of feeding, group of shrimps were challenged with virulent V. harveyi. After the respective days of feeding, haematological and immunological changes were studied. The parameters including total haemocyte count (THC), coagulase activity, oxyhaemocyanin level, prophenoloxidase, intracellular superoxide anion production, lysozyme, phagocytosis and bacterial agglutinin had significantly (P ≤ .001) increased in the experimental groups in comparission with the control diet fed shrimps. The anti-V. h IgY coated diets helped to reduce the Vibrio load and boosted the immune system in F. indicus's against V. harveyi challenge. The research work shows the potential applications of egg yolk antibodies as anti-bacterial prophylactic uses for infectious diseases and suggests an edible antibody concept as an alternative to conventional antibiotics.

Indirubin improves antioxidant and anti-inflammatory functions in lipopolysaccharide-challenged mice.

Indirubin, a traditional Chinese medicine formulation from the Muricidae family, has been reported to exhibit abroad anti-cancer and anti-inflammation activities and mediate nuclear factor-κB (NF-κB) signal. Thus, this study aimed to investigate the protective effects of indirubin on LPS-induced acute lung injury and the potential mechanism in mice. The results showed that LPS treatment caused oxidative stress and inflammation in mice. Indirubin alleviated LPS-caused oxidative stress and inflammation via reducing MDA abundance and IL-1ß and TNF-α expressions in mice. Meanwhile, indirubin improved lung NO production and inhibited NF-κB activation caused by LPS exposure. In conclusion, indirubin alleviated LPS-induced acute lung injury via improving antioxidant and anti-inflammatory functions, which might be associated with the NO and NF-κB signals.

Failure of Passive Immune Transfer in Calves: A Meta-Analysis on the Consequences and Assessment of the Economic Impact.

Low colostrum intake at birth results in the failure of passive transfer (FPT) due to the inadequate ingestion of colostral immunoglobulins (Ig). FPT is associated with an increased risk of mortality and decreased health and longevity. Despite the known management practices associated with low FPT, it remains an important issue in the field. Neither a quantitative analysis of FPT consequences nor an assessment of its total cost are available. To address this point, a meta-analysis on the adjusted associations between FPT and its outcomes was first performed. Then, the total costs of FPT in European systems were calculated using a stochastic method with adjusted values as the input parameters. The adjusted risks (and 95% confidence intervals) for mortality, bovine respiratory disease, diarrhoea and overall morbidity in the case of FPT were 2.12 (1.43-3.13), 1.75 (1.50-2.03), 1.51 (1.05-2.17) and 1.91 (1.63-2.24), respectively. The mean (and 95% prediction interval) total costs per calf with FPT were estimated to be €60 (€10-109) and €80 (€20-139) for dairy and beef, respectively. As a result of the double-step stochastic method, the proposed economic estimation constitutes the first estimate available for FPT. The results are presented in a way that facilitates their use in the field and, with limited effort, combines the cost of each contributor to increase the applicability of the economic assessment to the situations farm-advisors may face. The present economic estimates are also an important tool to evaluate the profitability of measures that aim to improve colostrum intake and FPT prevention.

Comprehensive Mechanism Analysis of Mesoporous-Silica-Nanoparticle-Induced Cancer Immunotherapy.

A plain mesoporous silica nanoparticle without any immunomodulatory molecules significantly enhances anticancer immunity in vivo. Comprehensive mechanism of mesoporous-silica-nanoparticle-induced cancer immunotherapy is analyzed in this paper. The mesoporous silica nanoparticle promotes both Th1 and Th2 immune responses, as it accelerates lymphocytes proliferation, stimulates IFN-γ, IL-2, IL-4, and IL-10 cytokine secretion by lymphocytes ex vivo, and increases IgG, IgG1, IgG2a, IgM, and IgA antibody titers in mice serum compared with those of alum and adjuvant-free groups. Moreover, the mesoporous silica nanoparticle enhances effector memory CD4(+) and CD8(+) T cell populations in three most important immune organs (bone marrow, lymph node, and spleen) of mice compared with those of alum and adjuvant-free groups three months after adjuvant injection. The present study paves the way for the application of mesoporous silica nanoparticle as immunoadjuvant for cancer immunotherapy.

IgY antibodies in human nutrition for disease prevention.

Oral administration of preformed specific antibodies is an attractive approach against infections of the digestive system in humans and animals in times of increasing antibiotic resistances. Previous studies showed a positive effect of egg yolk IgY antibodies on bacterial intoxications in animals and humans. Immunization of chickens with specific antigens offers the possibility to create various forms of antibodies. Research shows that orally applied IgY's isolated from egg yolks can passively cure or prevent diseases of the digestive system. The use of these alternative therapeutic drugs provides further advantages: (1) The production of IgY's is a non-invasive alternative to current methods; (2) The keeping of chickens is inexpensive; (3) The animals are easy to handle; (4) It avoids repetitive bleeding of laboratory animals; (5) It is also very cost effective regarding the high IgY concentration within the egg yolk. Novel targets of these antigen specific antibodies are Helicobacter pylori and also molecules involved in signaling pathways in gastric cancer. Furthermore, also dental caries causing bacteria like Streptococcus mutans or opportunistic Pseudomonas aeruginosa in cystic fibrosis patients are possible targets. Therefore, IgY's included in food for human consumption may be able to prevent or cure human diseases.

Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers.

BACKGROUND: Obesity in pregnancy is associated with systemic inflammation, immunological changes and adverse maternal-fetal outcomes. Information on the association between maternal obesity and breast milk composition is scarce. This study describes changes and relationships between biochemical and immunological parameters of colostrum and serum of overweight and obese women. METHODS: Colostrum and blood samples were collected from 25 normal weight, 24 overweight and 19 obese women for determination of glucose, total protein, triglycerides, cholesterol, immunoglobulins, complement proteins (C3 and C4), fat and calorie content and C-reactive protein (CRP). RESULTS: Glucose was higher in colostrum of obese women (p = .002). In normal weight and obese women, total protein content was higher in colostrum than in serum (p = .001). Serum triglycerides (p = .008) and cholesterol (p = .010) concentrations were significantly higher in overweight and obese women than in their normal weight counterparts, but in colostrum their concentrations were similar across the three groups. Secretory IgA (sIgA) in colostrum and IgA in serum concentrations were significantly higher (p = .001) in overweight and obese mothers, whereas IgG and IgM concentrations did not vary among the groups (p = .825). Serum C3 (p = .001) and C4 (p = .040) concentrations were higher in obese women. No differences in colostrum complement proteins were detected among the groups. Calorie content (p = .003) and fat (p = .005) concentrations in colostrum and serum CRP (p = .002) were higher in obese women. CONCLUSIONS: The results corroborate the hypothesis that colostrum of overweight and obese women undergoes biochemical and immunological changes that affect its composition, namely increasing glucose concentrations, calorie content, fat and sIgA concentrations.