Relative Thymus Research Articles

Effects of Kluyveromyces marxianus supplementation on immune responses, intestinal structure and microbiota in broiler chickens.

To investigate the effects of Kluyveromyces marxianus on immune responses, intestinal structure and microbiota in broilers, 840 1-d-old broiler chicks were randomly divided into seven groups (eight replicates) and were fed basal diets without or with 0.25, 0.50, 1.0, 1.5, 2.0, and 2.5 g/kg of K. marxianus (2.0×1010 CFU/g). Serum and intestine samples were collected at 21 d of age. The results showed that increasing K. marxianus addition linearly reduced feed conversion ratio but linearly elevated relative thymus weight, as well as quadratically increased serum lysozyme and IgG levels, with the medium dose (1.0 g/kg) being the most effective. The ratio of villus height to crypt depth of jejunum and ileum, ileal villus height and sucrase activity, as well as the mRNA expression of ileal mucin-2, claudin-1 and sodium glucose cotransporter 1 linearly responded to the increasing K. marxianus addition. Supplemental K. marxianus at low (0.5 g/kg), medium (1.5 g/kg) and high (2.5 g/kg) dose all decreased the abundance of phylum Cyanobacteria, increased the abundance of phylum Firmicutes and genus Lactobacillus in ileum. The high dose of K. marxianus addition also reduced the abundance of order Rickettsiales and Pseudomonadales along with species Acinetobacter junii. Ileal bacterial communities between K. marxianus-treated and untreated groups formed distinctly different clusters. In summary, K. marxianus supplementation benefits feed efficiency and immune function, as well as intestinal structure in broilers, which might be attributed to the improved ileal microbial structure. Supplemental K. marxianus at high dose (2.5 g/kg) was more effective for feed efficiency and intestinal health of broilers, while the innate immunity was optimized at a medium dose (1.0 g/kg).

Effects of dietary fat source and supplemental lysophosphatidylcholine on performance, immune responses, and ileal nutrient digestibility in broilers fed corn/soybean meal- or corn/wheat/soybean meal-based diets

Two separate experiments were conducted to investigate the effect of different fat sources and a supplemental exogenous emulsifier (lysophosphatidylcholine, LPC) on growth performance, antibody production titers, and ileal nutrient digestibility in broiler chicks fed with different basal diets. A total of 288 one-day-old Ross 308 chicks were used for each trial (6 dietary treatments based on 3 × 2 factorial arrangements of treatments in both trials) with 4 replicates of 12 birds each. Dietary treatments consisted of 3 different fat sources (soy oil, SO; soy free fatty acids, SFFA; and palm fat powder, PFP) and 2 LPC levels (0 and 0.1% of diet), which were evaluated with 2 different basal diets (corn/soybean meal-based diets in Exp. 1, or corn/wheat/soybean meal-based diets in Exp. 2). In Exp. 1, average daily feed intake (ADFI) was increased (P < 0.01) in birds fed PFP diets compared with those fed SO or SFFA diets. Although supplemental LPC decreased (P < 0.01) ADFI, the birds fed SFFA diets had the greater ADFI at the presence of LPC (fat source × LPC, P < 0.01). Dietary supplementation of LPC caused a 4.6% improvement (P < 0.001) in average daily weight gain (ADWG) and consequently improved (P < 0.01) feed conversion ratio (FCR). Supplemental LPC was more effective in increasing ADWG in SFFA-containing diets, resulted in a significant (P < 0.01) dietary fat source × LPC interaction. Dietary inclusion of LPC increased (P < 0.01) bursa weight and improved (P < 0.05) antibody production titers against sheep red blood cells and Newcastle disease virus during primary responses. Ileal digestibility of ether extract (EE) was improved (P < 0.05) in birds fed diets containing SO as compared with those fed PFP diets; dietary LPC supplementation, however, had no marked effect on ileal nutrient digestibility. In Exp. 2, ADWG was greater (P < 0.05) in birds fed SO-containing diets compared with PFP-supplemented broiler chicks. Furthermore, dietary supplementation with LPC improved (P < 0.05) FCR value by 2.1%. Relative thymus weight was greater (P < 0.05) in birds fed LPC-supplemented diets than those fed unsupplemented diets. Supplemental LPC increased (P < 0.05) Gumboro antibody titer, and the lowest antibody response was allotted to the birds fed PFP diets. The greatest (P < 0.05) EE digestibility was assigned to the birds fed SO and SFFA diets. The present findings showed that birds fed SFFA-containing diets had similar performance as SO birds, and supplemental LPC improved overall performance especially in SFFA-fed birds.

Efficacy of mixed adsorbent in ameliorating ochratoxicosis in broilers fed ochratoxin A contaminated diets

The current study was conducted to evaluate the ability of mixed adsorbent (Na-MMT + YCW) for the preventing effect of Ochratoxin A in broiler productivity, biochemical parameters, histochemical changes and OTA residues. A total of 96 broiler chicks were grouped in three experimental and one control group (24 chicks in each group, 3 replicates each). Birds were fed basal dietary or that with Ochratoxin A and mixed adsorbent (Na-MMT + YCW) to determine the effect of this compound during mycotoxicoses. When compared with the controls, feed: gain (F/G) were significantly higher for broilers fed diets containing OTA alone (p < .05). No differences were found between the F/G of broiler chickens fed diets without OTA and those of chickens fed mixed adsorbent. The diet containing 2 mg OTA/kg without adsorbents added increased relative liver, kidney, spleen weights and decreased relative thymus, bursa weights. Alterations in the levels of serum TP, ALB, GLB, BUN and enzymatic activity of ALT, AST, ALP and GGT were observed for OTA diets, and moderate protection was provided by the sorbent. Supplementing mixed adsorbent group (Na-MMT + YCW) showed intestinal villus height and crypt depth similar to control chicks, and a significant reduction residue in livers and kidney tissue, as well as a significantly higher OTA content in the faeces compared with OTA- group were recorded. These results suggest that effects of OTA treatment were ameliorated when mixed adsorbent was used in the broiler chick diets.

Purification, characterization, and antitumor activity of a novel glucan from the fruiting bodies of Coriolus Versicolor.

Cancer is one of the most common causes of deaths worldwide. Herein, we report an efficient natural anticancer glucan (CVG) extracted from Coriolus Versicolar (CV). CVG was extracted by the hot water extraction method followed by ethanol precipitation and purified using gas exclusion chromatography. Structural analysis revealed that CVG has a linear α-glucan chain composed of only (1→ 6)-α-D-Glcp. The antitumor activity of CVG on Sarcoma-180 cells was investigated in vitro and in vivo. Mice were treated with three doses of CVG (40, 100, 200 mg/kg body weight) for 9 days. Tumor weight, relative spleen, thymus weight, and lymphocyte proliferation were studied. A significant increase (P< 0.01) in relative spleen and thymus weight and a decrease (P< 0.01) in tumor weight at the doses of 100 and 200 mg/kg were observed. The results obtained demonstrate CVG has antitumor activity towards Sarcoma-180 cells by its immunomodulation activity.

Higher susceptibility of somatostatin 4 receptor gene-deleted mice to chronic stress-induced behavioral and neuroendocrine alterations

The somatostatin 4 receptor (sst4) is widely expressed in stress-related brain areas (e.g. hippocampus, amygdala) and regulates the emotional behavior in acute situations. Since its importance in chronic stress-induced complex pathophysiological alterations is unknown, we investigated the involvement of sst4 in the responsiveness to chronic variable stress (CVS). Sstr4 gene-deficient (Sstr4−/−) mice and their wildtype counterparts (Sstr4+/+) were used to examine the behavioral and neuroendocrine alterations as well as chronic neuronal activity (FosB expression) changes in response to CVS. In Sstr4+/+ mice, there was no behavioral response to the applied CVS paradigm. In contrast, immobility time in the tail suspension test increased after the CVS in the knockouts. In the forced swim test, Sstr4−/− animals showed increased baseline immobility and then it decreased after the CVS. Light–dark box and open field test behaviors and sucrose preference did not respond to the stress in the knockouts. Adrenal weights increased and thymus weights decreased in both Sstr4+/+ and Sstr4−/− mice demonstrating the effect of chronic stress. The relative adrenal weight of stressed knockouts increased to a greater extent, while relative thymus and body weights decreased only in the Sstr4−/− mice. Basal plasma corticosterone concentrations did not change after the CVS in either genotype. FosB immunopositivity in the central and basolateral amygdaloid nuclei was enhanced in stressed knockouts, but not in wild types. This is the first evidence that sst4 activation is involved in the behavioral and neuroendocrine alterations induced by chronic stress with a crucial role of plastic changes in the amygdala.

Immunohistochemical Detection of FOXP3 Shows Stimulatory Effect of Metformin on Thymus Regulatory T-Cells in Type 2 Diabetic Mice

Metformin is an adjuvant drug used in the treatment of obesity and diabetes, two conditions associated with stress and chronic inflammation that affects thymus structure and function. Recent evidence suggests a complex role of metformin in thymic homeostasis. The study was designed to develop an animal model of obesity and type 2 diabetes, and treat it with metformin to evaluate its effects on the thymus. In addition, its general effects on body weight and blood glucose level were also investigated. Over a period of 6 weeks, 30 albino male mice (4-5 weeks) were fed either regular chow (control group, N=10) or high fat diet (obese group). The obese group was then subjected to low dose streptozotocin induction of diabetes and divided into two subgroups, one of which was treated with metformin (N=10) while the other was not (N=10). Body weight, random blood sugar, relative thymus weight were recorded. Thymic tissue sections were stained with H &amp; E to study general histology and with single immunohistochemical stain to detect regulatory T-cell using FOXP3 marker. Thymic corticomedullary ratio and regulator cell frequency were calculated. Metformin was successful in reducing body weight and blood glucose levels in treated animals. The thymus had higher relative weight and less cortical cellularity but more frequently counted regulatory cells. Untreated animals showed signs of thymic involution but increased corticomedullary ration in response to reduced regulator cell counts. Metformin has both direct and indirect effects in correcting metabolic abnormalities associated with obesity and diabetes. These effects are anti-inflammatory and may be responsible for stimulation of thymic immunosuppressive cells. Contrariwise, obesity and diabetes have detrimental effects on thymus structure and homeostasis.

Immune-Enhancing Effects of a High Molecular Weight Fraction of Cynanchum wilfordii Hemsley in Macrophages and Immunosuppressed Mice.

The objective of this study was to investigate the immune-enhancing activity of a high molecular weight fraction (HMF) of Cynanchum wilfordii in RAW 264.7 macrophages and the cyclophosphamide (CYC)-induced mouse model of immunosuppression. To identify the bioactive substances of HMF, a crude polysaccharide (HMFO) was obtained and treated with sodium periodate (an oxidation agent) or digested with protease. In macrophages, HMF treatment enhanced the production of nitric oxide (NO) and cytokines (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β)), as well as phagocytic ability. In CYC-immunosuppressed mice, HMF improved relative spleen and thymus weights, natural killer (NK) cell activity, and splenic lymphocyte proliferation. These increases in NO and cytokines were mediated by up-regulation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Periodate treatment, but not protease treatment, decreased the immune-enhancing activity of HMFO, suggesting that polysaccharides are the active ingredients in C. wilfordii extract.

ФУНКЦІОНУВАННЯ ІМУННОЇ СИСТЕМИ ПЕРЕПЕЛІВ В РІЗНІ ПЕРІОДИ ПОСТНАТАЛЬНОГО ОНТОГЕНЕЗУ

In the article are given results concerning main morphometric characteristics of immunogenesis organs in “Pharaon” breed of quails of industrial raising during different periods of postnatal ontogenesis. It is established that highest numeric values of relative mass index and thymus, Fabricius bursa, spleen of quail species «Pharaoh» in 5 days age. It was found that the vast mass of the thymus quail increased to 33 days of life, Fabricius bursa – up to 53 days of life and spleen – up to 240 days of life. It was established that with the egg (53 and 75 day life) and 240–day old quail in the relative weight and thymus index decreased five times (p &lt; 0,01 – 0,001) seminary Fabricius bursa – three times (p &lt; 0,05 – 0,01). It was investigated that the relative reduction of mass and spleen index in three quails from 20 to 240 days of life. The data indicate a change of immunological reactivity quail in different age periods, especially in the productive oviparous period and the beginning age involution of the thymus, Fabricius bursa. The possible reduction of the seminary index below 1.0 in quails from 75 to 240 days of life may indicate suppression of B–immunity, that reduce the formation of B – lymphocytes. The reduction of the relative weight and spleen index quail tripled from 20 to 240 days of life on the background of declining same period of the thymus and Fabricius bursa may indicate a compensatory reduction of the organism poultry.

Involvement of hypoxia-inducible factor-1 α (HIF-1α) in inhibition of benzene on mouse hematopoietic system

ABSTRACTBenzene is an occupational and environmental pollutant that damages the hematopoietic system through oxidant mechanisms. The aims of this study were to assess the role of oxidation in benzene-mediated damage by determination of the levels of reactive oxygen species (ROS) and to evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in this process. C57BL/6 mice were exposed to benzene at varying concentrations of 60, 150, or 300 mg/kg/d for 15 d. Mice in the benzene groups displayed weight loss, and hematologic consequences including decreased red and white blood cell counts, reduced platelet count, diminished hemoglobin content, and lower number of hematopoietic stem cells in bone marrow (BM). There was an elevated proportional neutrophil count and decrease in relative thymus weight. In BM there was a significant increase in ROS levels at 150 mg/kg benzene. However, as a result of diminished cellular viability, ROS levels were not markedly different between the 300-mg/kg benzene dose and the control, as the number of hematopoietic stem cells was reduced. HIF-1α expression and protein levels were decreased in BM cells at all doses of benzene. In conclusion, data indicated that HIF-1α may be involved in benzene-induced inhibition of mouse hematopoiesis and that oxidative stress may play a role in the observed toxicity.

The effects of enrichment novelty versus complexity in cages of group-housed rats (Rattus norvegicus)

Although experimental work on environmental enrichment has answered many important questions, it is not yet known whether beneficial effects of enrichment are more strongly influenced by regular provision of novel objects, or by the diversity of objects present at any one time. In a five-replicate study, 80 newly weaned male Wistar rats were housed in groups of four in: a ‘novelty’ condition (NC) in which five copies of the same object were provided in the home cage during the first week of the study followed by five copies of a different, novel, object over each of the next 4 weeks; a ‘complexity’ condition (CC) in which one example of each of the five objects used in NC was always present in the cage across the 5-week study period. Behaviour was collected in two 2-h sessions every week, once during the light phase of the light/dark cycle and once during the dark phase. Body weight and weight gain were measured over the five weeks and organ weights were recorded post-mortem. Rats in the CC displayed elevated levels of measures suggestive of improved welfare such as sleep, enrichment-directed behaviour, enrichment contact, weight gain and relative thymus weight, and decreased levels of indicators denoting poor welfare including aggression, awake-non active and audible vocalizations. It appears that CC may have the potential to increase the frequency and diversity of behaviours, to express different types of behaviour when desired, and to augment the ability of the animals to exert some control over their environment, findings that may improve their welfare. Provision of novelty per se in the absence of diversity of objects at any one time seems to be less beneficial. Order (replicate) effects in the NC group indicated that responses of the animals towards the enrichment regimen appeared to depend on the type of object supplied, thus drawing attention to the importance of object characteristics when designing enrichment protocols for laboratory animals.

Assessment of the Mitigative Capacity of Dietary Zinc on PCB126 Hepatotoxicity and the Contribution of Zinc to Toxicity.

Hepatic levels of the essential micronutrient, zinc, are diminished by several hepatotoxicants, and the dietary supplementation of zinc has proven protective in those cases. 3,3',4,4',5-Pentachlorobiphenyl (PCB126), a liver toxicant, alters hepatic nutrient homeostasis and lowers hepatic zinc levels. The current study was designed to determine the mitigative potential of dietary zinc in the toxicity associated with PCB126 and the role of zinc in that toxicity. Male Sprague-Dawley rats were divided into three dietary groups and fed diets deficient in zinc (7 ppm Zn), adequate in zinc (30 ppm Zn), and supplemented in zinc (300 ppm). The animals were maintained for 3 weeks on these diets, then given a single IP injection of vehicle or 1 or 5 μmol/kg PCB126. After 2 weeks, the animals were euthanized. Dietary zinc increased the level of ROS, the activity of CuZnSOD, and the expression of metallothionein but decreased the levels of hepatic manganese. PCB126 exposed rats exhibited classic signs of exposure, including hepatomegaly, increased hepatic lipids, increased ROS and CYP induction. Liver histology suggests some mild ameliorative properties of both zinc deficiency and zinc supplementation. Other metrics of toxicity (relative liver and thymus weights, hepatic lipids, and hepatic ROS) did not support this trend. Interestingly, the zinc supplemented high dose PCB126 group had mildly improved histology and less efficacious induction of investigated genes than did the low dose PCB126 group. Overall, decreases in zinc caused by PCB126 likely contribute little to the ongoing toxicity, and the mitigative/preventive capacity of zinc against PCB126 exposure seems limited.

LPS reduces BDNF and VEGF expression in the structures of the HPA axis of chronic social stressed female rats

Imbalance of brain neural circuitry induced by chronic stress leads to dysregulation of the HPA axis and dysfunction of neuroplasticity. The aim of the study was to investigate the influence of acute immunostimulation on the expression and protein level of BDNF and VEGF in the hypothalamus, pituitary and plasma of female rats subjected to chronic social instability stress. Rats were subjected to 4-week stress procedure, including phases of isolation and crowding, alternated in an unpredictable manner. On the last experimental day, the rats in the estrus phase were injected ip. with LPS (1mg/kg). All experiments were performed on females being in the same phase of the estrus cycle to avoid alterations in neurotrophin expression. An increase in relative adrenal and thymus weights in the stressed rats were observed. Chronic stress affected more strongly VEGF but not BDNF in the hypothalamus and pituitary gland. In the stressed rats, LPS decreased BDNF and VEGF mRNA levels in both structures and plasma BDNF concentrations. Optical density of VEGF immunoreactivity in the supraoptic nucleus was increased after LPS administration in the stressed rats as compared to the saline-treated stressed group. It may be assumed that chronic social stress makes the SOR neurons sensitive to a peripheral proinflammatory stimulus. Our results indicate that chronic stress enhances vulnerability of BDNF and VEGF response to neuroinflammation in the examined structures, which may be one of the reasons for its role in triggering affective diseases.

Antitumor and immunomodulatory activity of a water-soluble polysaccharide from Grifola frondosa

Grifola frondosa has long been known and respected as a medically important fungus. This study investigated the characterization, antitumor and immunomodulatory activity of a polysaccharide named GP11 purified from G. frondosa. The results revealed that GP11 was composed of →1)-d-Manp-(6→,→1)-d-Glcp-(4→,→1)-d-Galp-(6→and→2,3,6)-d-Glcp-(1→, with branches attached at O-2,3 of 1,2,3,6-linked Glcp residues and terminal T-Glcp. GP11 exhibited indirect cytotoxic activity against HepG-2 cells in vitro, and it significantly inhibited the growth of Heps cells in vivo. GP11 increased the relative thymus and spleen weights as well as serum tumor necrosis factor-alpha and interleukin-2 levels. GP11 stimulated tumoricidal activity and the production of nitric oxide (NO), TNF-α and interleukin-1β, and it also stimulated the protein expression of iNOS and mRNA expression of iNOS and TNF-α. TLR-4 is a potential receptor for GP11-mediated macrophage activation. The results suggested that the antitumor activity of GP11 may be due to the improvement of immune functions through the TLR-4-mediated up-regulation of NO and TNF-α.

ВПЛИВ ГРИБА GANODERMA LUCIDUM (CURT.:FR.) P. KARST. НА ГУМОРАЛЬНУ ІМУННУ ВІДПОВІДЬ У МИШЕЙ ЛІНІЇ CBA/CA З ВТОРИННИМ ІМУНОДЕФІЦИТОМ

&lt;p&gt;&lt;strong&gt;INFLUENCE OF MUSHROOM GANODERMA LUCIDUM (CURT.: FR.) P. KARST. ON THE HUMORAL IMMUNE RESPONSE IN MICE LINE CBA / Ca WITH SECONDARY IMMUNODEFICIENCY.&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;V.T. Pidchenko*, I.V. Nizhenkovska*, N.G. Bychkova*, N.A. Bisko**, A.Y. Rodnichenko***&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;*Bogomolets National medical university, Kyiv&lt;/p&gt;&lt;p&gt;**M.G. Kholodny Institute of Botany NASU, Kyiv&lt;/p&gt;&lt;p&gt;***The State Institute of Genetic and Regenerative MedicineNAMSUkraine, Kyiv&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary:&lt;/strong&gt; The article shows the results of the investigation of the influence of biomass powder of mushroom Ganoderma lucidum on the humoral immune response in mice line CBA / Ca in terms of the simulated secondary immunodeficiency. To simulate the immunodeficiency was used the immunosuppressant cyclophosphamide, which was administered once a dose of 150 mg / kg, intraperitoneally, the first day of the experiment. Results of the study show that the application of Ganoderma Lucidum biomass powder in mice line CBA / Ca with induced immune deficiency, causes a significant increase in the number of antibody-producing cells in the spleen and antibody levels in serum.&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key words:&lt;/strong&gt; Ganoderma lucidum, humoral immune response, cyclophosphamide, immunodeficiency.&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction.&lt;/strong&gt; Searching and development of remedies of natural origin is an actual problem today. In recent decades, basidiomycetes and biologically active substances extracted from them, attracted attention of scientists in Asia andNorth America. Ganoderma lucidum, a native biosidiomycetous fungus, has been used inChina,Japan andKorea to prevent and treat bronchitis, chronic hepatitis, hypertension, atherosclerosis, tumor growth and immunological disorders for over 2000 years. The influence of biomass powder of mushroom Ganoderma lucidum, grown by submerged cultivation, at various immunity in immunodeficient conditions is not studied. Therefore the aim of our study was to determine the influence of biomass powder of mushroom Ganoderma lucidum on humoral immune response in mice with secondary immunodeficiency in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods.&lt;/strong&gt; The biomass of mushroom Ganoderma lucidum was grown by submerged cultivation. To simulate the immunodeficiency was used the immunosuppressant cyclophosphamide, which was administered once a dose of 150 mg / kg, intraperitoneally, the first day of the experiment. The number of antibody-producing cells in the spleen and antibody levels in serum were discovered. Statistical analysis of the results was performed using Student`s t-test.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results and discussion.&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;The introduction of biomass powder of mushroom Ganoderma lucidum for 10 days to mice line CBA / Ca with secondary experimental immunodeficiency causes a significant increase in the number of cells in femur.&lt;/p&gt;&lt;p&gt;The recovery of thymus weight, relative thymus weight, thymus settlement index and number of lymphoid cells in the organ to the level of data in a group of control mice after the administration of biomass powder was not found.&lt;/p&gt;&lt;p&gt;The introduction of biomass powder of mushroom Ganoderma lucidum to mice line CBA / Ca with secondary experimental immunodeficiency causes a significant increase in the relative number of antibody-producing cells in the spleen in 2 times, the absolute number of antibody-producing cells in 2,1 times compared with the group of mice treated with cyclophosphamide. The antibody levels increase in 6,7 times (hemolysin titer) and 2,4 times (hemagglutinin titer).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions.&lt;/strong&gt; Thus, the results of the study show that the introduction of biomass powder fungus Ganoderma lucidum to mice line CBA / Ca with secondary experimental immunodeficiency causes a significant increase in the number of antibody-producing cells in the spleen and antibody levels in serum, which may indicate the immunomodulatory effect of biomass powder of fungus Ganoderma lucidum on humoral immune response.&lt;/p&gt;

Impact of certain immunomodulators on LPS-induced hematotoxicity

The present study aimed to explore the extent to which immunomodulators may protect against Klebsiella pneumonia lipopolysaccharide (K pn LPS) toxicity. Two immunomodulators (levamisole and DDB) were utilized in the present work. The study was carried out on male Sprague Dawley rats, and animals were divided into four groups: One group was injected with saline intraperitoneally (i.p.) and served as a control group. The other three groups were subcutaneously daily injected with repetitive doses of K pn LPS (10, 10, 20, 20 and 40 µg/kg, i.p., for 5 consecutive days). Two of these K pn LPS-injected groups were daily co-treated with either levamisole (3 mg/kg, for 5 consecutive days, p.o) or DDB (6 mg/kg, for 5 consecutive days, p.o). At the end of the experiment, the effects of the given treatment were evaluated as regarding relative spleen and thymus weights, certain hematological changes (total and differential white blood cells count (WBCs), red blood cells count (RBCs), platelet count (PLAT), hemoglobin content (Hb), bone marrow cell count, as well as the histopathological changes in each of the spleen, thymus and bone marrow. The obtained results revealed that K pn LPS induced body weight loss, splenomegaly, thymic atrophy, leukopenia and lymphocytopenia. Each of bone marrow cells count and reticulocytes and eosinophil percentages were noticeably decreased after 5 days of K pn LPS administration. Each of the utilized drugs potentiated LPS-induced lymphocytopenia and increased segmented cells. However, DDB co-administration prior to K pn LPS injection could prevent the drop in bone marrow nucleated cells count, total WBCs, reticulocytes count and eosinophils differential count restoring them to their normal ranges. The histopathological examination of thymus, spleen and bone marrow of rats treated with either of the two utilized immunomodulators confirmed the above-mentioned results. Finally, the study reveals that DDB co-administration exerts more pronounced modulatory effect on LPS-induced hematotoxicity.

Extraction, characterization of a Ginseng fruits polysaccharide and its immune modulating activities in rats with Lewis lung carcinoma

In this study, one polysaccharide (GFP1), with an average molecular weight of 1.4×105Da, was isolated from Ginseng fruits. GFP1 was composed of galactose, glucose, rhamnose, and arabinose in a molar ratio of 6.1:2.0:1.1:3.2, and had a backbone mainly consisting of (1→6)-linked-Galp, (1→3,6)-linked-Galp and (1→3,6)-linked-Glcp residues, which was terminated with terminal (1→)-linked-Araf or -Rhap attached to O-3 position of (1→3,6)-linked-Galp and (1→3,6)-linked-Glcp. We also evaluated the effect of GFP1 on anti-tumor immune response in Lewis lung carcinoma (LLC)-bearing mouse model and explored the possible mechanism. GPF1 could significantly inhibit tumor growth and lung metastasis in vivo, increase the relative spleen and thymus weight, promote ConA or LPS-induced spleen lymphocytes proliferation, elevate the activities of NK cell in spleen, and increase the serum concentration of interleukin-2 (IL-2) and interferon-γ (IFN-γ), as well as the ratio of CD4+/CD8+ in LLC-bearing mice. All these findings implied that GFP1 could effectively inhibit tumor growth and lung metastasis via activating immune function and provide insights into the mechanism of GFP1 in the prevention and treatment of lung cancer.

Structure characterization and antitumor activity of a polysaccharide from the alkaline extract of king oyster mushroom.

A water-soluble polysaccharide, designated as KOMAP, was isolated and purified from the alkaline extract of king oyster mushroom, which was composed of glucose (Glc), mannose (Man) and arabinose (Ara) in a molar ratio of 6.2:2.1:2.0. It had an average molecular weight of 2.1×10(4)Da. GC-MS analysis revealed that KOMAP was a linear structure of the polymer with a backbone composed of β-1,4-linked glucopyranosyl and β-1,3,6-linked mannopyranosyl units, which was terminated with α-1-linked arabinofuranosyl unit at C-6 position of β-1,3,6-linked mannopyranosyl residue along the main chain in the ratio of 3.1:1. The results in the animal experiment showed that 50, 100 and 200mg/mL of KOMAP not only inhibited the tumor growth, but also increased relative thymus and spleen indices, LPS- or ConA-induced lymphocytes proliferation, and serum cytokine IL-2, TNF-α, and IFN-γ levels, as well as the activities of NK cells and CTLs in spleen of Renca tumor-bearing mice. In summary, our data indicate that the KOMAP exerts effective immunoregulatory and anti-tumor activities in vivo.

Increased levels of standardized ileal digestible threonine attenuate intestinal damage and immune responses in Escherichia coli K88+ challenged weaned piglets

This study was conducted to investigate the effects of graded levels of standardized ideal digestible threonine (SIDT) on the small intestinal morphology and immune responses of Escherichia coli K88+ challenged weaned piglets. Thirty-six crossbred (Large White×Landrace) barrows, with an initial BW of 7.34±0.55kg and weaned at 21d, were assigned to 1 of 6 treatments according to a 3 (3.7, 7.5 or 11.1g/kg dietary SIDT content)×2 (non-challenged or challenged) factorial arrangement. On d 16, half of the piglets in each SIDT treatment were orally challenged with 10mL E. coli K88+ culture (1×109CFU/mL), while the other half were orally inoculated with the same amount of phosphate buffer (PBS). On d 18 (on 2d after E. coli challenged), the pigs were killed and blood and intestinal samples were collected. The average daily gain (ADG) and feed conversion ratio (FCR) of piglets receiving the 7.5 and 11.1g/kg SIDT diets were significantly improved (P<0.01) during pre-challenge (0–16d), post-challenge (16–18d) and over the entire experiment (0–18d) compared with pigs fed the 3.7g/kg SIDT diet. E. coli K88+ challenge markedly decreased (P<0.05) ADG and FCR of piglets compared with PBS. Increasing dietary SIDT increased the relative thymus body weight of non-challenged piglets while the relative body weight of challenged piglets was not affected by SIDT. Increasing of dietary SIDT significantly increased (P<0.05) lymphocyte proliferation under challenge. Compared with pigs fed the 3.7g/kg SIDT diet, the interleukin-1β concentration significantly (P<0.05) decreased, and the interleukin-6 concentration significantly (P<0.05) increased in the jejunum of piglets fed the 7.5 and 11.1g/kg SIDT diets. It was observed that an interaction between dietary SIDT and E. coli challenge on the levels of mucosal IgA and interleukin-1β (P<0.05). Increasing SIDT increased the duodenal villus width in non-challenged piglets and there was no difference among challenged piglets. Duodenal villi height decreased (P=0.05) after E. coli challenge. Piglets receiving either the 7.5 or 11.1g/kg SIDT diets had increased villi heights and villi height to crypt depth ratio (P<0.05), and decreased crypt depth (P<0.05) in jejunum compared with the 3.7g/kg SIDT diet. Once challenged with E. coli K88+, villus height and villus height to crypt depth ratio of jejunal decreased (P<0.05). The interaction between challenge and dietary SIDT was observed in jejunal crypt depth and villus height to crypt depth ratio. Increasing dietary SIDT decreased the jejunal crypt depth and increased villus height to crypt depth ratio in non-challenged piglets. Moreover, the ileal crypt depth increased (P<0.05) and ileal villus height to crypt depth ratio decreased (P<0.05) after E. coli challenge. Collectively, these results indicate that appropriate dietary SIDT improved mucosal immune function and intestinal morphology of non-challenged pigs and also had beneficial effects in maintaining jejunal integrity and repairing villous damage caused by E. coli challenge. Our findings indicate that appropriate dietary SIDT levels need to be considered when formulating diets for weaned piglets in different physical status.

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10–50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

Correlation between Marek's disease virus pathotype and replication.

Marek's disease (MD) virus (MDV) is an alphaherpesvirus that causes MD, a lymphoproliferative disease in chickens. Pathotyping has become an increasingly important assay for monitoring shifts in virulence of field strains; however, it is time-consuming and expensive, and alternatives are needed to provide fast answers in the face of current outbreaks. The purpose of this study was to determine whether differences in virus replication between pathotypes that have been reported using a small number of virulent (v) and very virulent plus (vv+) MDV strains could be confirmed with a large collection of MD viruses. Based on pilot study data, bursa, brain, and lung samples were collected at 9 and 11 days postinoculation (dpi) from birds challenged with 1 of 15 MDV strains. The correlation between virus replication and virulence was confirmed between vMDV strains and higher virulent strains, but in most cases, there was no significant difference between very virulent (vv) and vv+MDV groups. At both 9 and 11 dpi, chickens infected with vv and vv+MDV had significantly lower body weights and relative thymus and bursa weights compared with chickens challenged with vMDV. However, similar to virus quantity, there was no significant difference between weights in birds challenged with vv or vv+MDV. The significant differences observed in maternal antibody negative (ab-) chickens were not significant in maternal antibody positive (ab+) chickens, demonstrating the requirement of ab- birds for this type of comparison. These data do not support the use of virus replication or organ weights as an alternative to pathotyping for discrimination between all three virulent MDV pathotypes but may be useful for determining a virus replication threshold to choose which field strains meet a minimum virulence to be pathotyped by traditional methods.