Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Ferric citrate-induced colonic mucosal damage associated with oxidative stress, inflammation responses, apoptosis, and the changes of gut microbial composition.

Ferric citrate (FC) has been used as an iron fortifier and nutritional supplement, which is reported to induce colitis in rats, however the underlying mechanism remains to be elucidated. We performed a 16-week study of FC in male healthy C57BL/6 mice (nine-month-old) with oral administration of Ctr (0.9 % NaCl), 1.25 % FC (71 mg/kg/bw), 2.5 % FC (143 mg/kg/bw) and 5 % FC (286 mg/kg/bw). FC-exposure resulted in colon iron accumulation, histological alteration and reduce antioxidant enzyme activities, such as glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), together with enhanced lipid peroxidation level, including malondialdehyde (MDA) level and 4-Hydroxynonenal (4-HNE) protein expression. Exposure to FC was associated with upregulated levels of the interleukin (IL)- 6, IL-1ß, IL-18, IL-8 and tumor necrosis factor α (TNF-α), while down-regulated levels of IL-4 and IL-10. Exposure to FC was positively associated with the mRNA and protein expressions of cysteine-aspartic proteases (Caspase)- 9, Caspase-3, Bcl-2-associated X protein (Bax), while negatively associated with B-cell lymphoma 2 (Bcl2) in mitochondrial apoptosis signaling pathway. FC-exposure changed the diversity and composition of gut microbes. Additionally, the serum lipopolysaccharide (LPS) contents increased in FC-exposed groups when compared with the control group, while the expression of colonic tight junction proteins (TJPs), such as Claudin-1 and Occludin were decreased. These findings indicate that the colonic mucosal injury induced by FC-exposure are associated with oxidative stress generation, inflammation response and cell apoptosis, as well as the changes in gut microbes diversity and composition.

Polysaccharide from Salviae miltiorrhizae Radix et Rhizoma Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease through Modulating Intestinal Microbiota-Related Gut-Liver Axis.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, thus treatments for it have attracted lots of interest. In this study, the Salviae miltiorrhizae Radix et Rhizoma (SMRR) polysaccharide was isolated by hot water extraction and ethanol precipitation, and then purified by DEAE anion exchange chromatography and gel filtration. With a high-fat-diet-induced obesity/NAFLD mouse model, we found that consumption of the SMRR polysaccharide could remarkably reverse obesity and its related progress of NAFLD, including attenuated hepatocellular steatosis, hepatic fibrosis and inflammation. In addition, we also reveal the potential mechanism behind these is that the SMRR polysaccharide could regulate the gut-liver axis by modulating the homeostasis of gut microbiota and thereby improving intestinal function.

TRIM67 Deficiency Exacerbates Hypothalamic Inflammation and Fat Accumulation in Obese Mice.

Obesity has achieved the appearance of a global epidemic and is a serious cause for concern. The hypothalamus, as the central regulator of energy homeostasis, plays a critical role in regulating food intake and energy expenditure. In this study, we show that TRIM67 in the hypothalamus was responsive to body-energy homeostasis whilst a deficiency of TRIM67 exacerbated metabolic disorders in high-fat-diet-induced obese mice. We found exacerbated neuroinflammation and apoptosis in the hypothalamus of obese TRIM67 KO mice. We also found reduced BDNF in the hypothalamus, which affected the fat sympathetic nervous system innervation and contributed to lipid accumulation in adipose tissue under high-fat-diet exposure. In this study, we reveal potential implications between TRIM67 and the hypothalamic function responding to energy overuptake as well as a consideration for the therapeutic diagnosis of obesity.

Pectic polysaccharide from Nelumbo nucifera leaves promotes intestinal antioxidant defense in vitro and in vivo.

In this study, the Nelumbo nucifera leaf polysaccharide (NNLP) was isolated by hot water extraction and ethanol precipitation. DEAE anion exchange chromatography and gel filtration were further performed to obtained the purified fraction NNLP-I-I, the molecular weight of which was 16.4 kDa. The monosaccharide composition analysis and linkage units determination showed that the fraction NNLP-I-I was a pectic polysaccharide. In addition, the NMR spectra analysis revealed that NNLP-I-I mainly consisted of a homogalacturonan backbone and rhamnogalacturonan I, containing a long HG region and short RG-I region, with AG-II and 1-3 linked rhamnose as side chains. The biological studies demonstrated that NNLP-I-I displayed antioxidant properties through mediating the Nrf2-regulated intestinal cellular antioxidant defense, which could protect cultured intestinal cells from oxidative stress and improve the intestinal function of aged mice.

New pectic polysaccharides from Codonopsis pilosula and Codonopsis tangshen: structural characterization and cellular antioxidant activities.

BACKGROUND: Codonopsis pilosula and Codonopsis tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from the roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography. RESULTS: The core structures of both CPP-1 and CTP-1 comprise the long homogalacturonan region (HG) as the backbone and the rhamnogalacturonan I (RG-I) region as the side chains. CPP-1 has methyl esterified galacturonic acid units and a slightly lower molecular weight than CTP-1. Biological testing suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H2 O2 -induced oxidative stress by up-regulating nuclear factor-erythroid 2-related factor 2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of differences in their structures. CONCLUSION: All of the results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. © 2021 Society of Chemical Industry.

Protective Effect of Vitamin E on Cadmium-Induced Renal Oxidative Damage and Apoptosis in Rats.

Cadmium (Cd), a widely distributed heavy metal, is extremely toxic to the kidney. Vitamin E (VE) is an important antioxidant in the body. It is known that VE exerts a protective effect on renal oxidative damage caused by Cd, but the effect and mechanism of VE on apoptosis are not fully understood. Thus, we conducted this study to explore the protective effect of VE on Cd-induced renal apoptosis and to elucidate its potential mechanism. Thirty-two 9-week-old male Sprague-Dawley rats were randomly divided into four groups, namely control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl2), and VE + Cd (100 mg/kg VE + 5 mg/kg CdCl2), and received intragastric administration of Cd and/or VE for 4 weeks. The results showed that Cd exposure significantly reduced the weight of the body and kidney, elevated the accumulation of Cd in the kidney as well as the levels of BUN and Scr in serum, caused renal histological alterations, decreased the GSH and T-AOC contents and antioxidant enzyme (SOD, CAT, GSH-PX) activities, and increased renal MDA content. And the increased number of TUNEL-positive cells by Cd was accompanied by upregulated mRNA and protein expressions of apoptotic regulatory molecules (Bax, Caspase-3, GRP94, GRP78, Caspase-8) and downregulated Bcl-2 expressions. However, the combined treatment of Cd and VE could restore the above parameters to be close to those in the control rats. In conclusion, VE supplement could alleviate Cd-induced rat renal damage and oxidative stress through enhancing the antioxidant defense system and inhibiting apoptosis of renal cells.

Iron Overload Resulting from the Chronic Oral Administration of Ferric Citrate Impairs Intestinal Immune and Barrier in Mice.

Ferric citrate (FC) is an iron-containing phosphate binder used as a food additive for iron supplementation. To explore the potential effect of ferric citrate on intestinal epithelial function, in the present study, we administered the mice orally for 16 weeks with different doses of iron citrate (2.5 mg/day (1.25%), 5 mg/day (2.5%), and 10 mg/day (5.0%)). We found that the iron levels of serum and tissue significantly increased, which caused the body to be in an iron overload state; meanwhile, the villus height, the ratio of villus height to crypt depth, and the number of intraepithelial lymphocytes and goblet cells in jejunum all decreased. Iron overload upregulated the pro-inflammatory cytokines (IL-1ß, IL-2, IL-6, TNF-ɑ), while downregulated the anti-inflammatory cytokines (IL-4, IL-10) and sIgA. Moreover, iron overload increased serum D-lactate (D-LA) levels and decreased tight junction proteins (claudin-1, occludin, and ZO-1), MUC-2, and TFF3. In addition, iron overload upregulated the content of MDA and protein carbonyl, while downregulated the activity and content of T-AOC, GSH-PX, SOD, CAT, and GSH. To sum up, the present results showed that long-term oral administration of FC resulted in iron overload, which consequently impaired intestinal immune and barrier function in mice. Meanwhile, the effect on intestinal damage may be highly related to the increase of oxidative stress in the jejunum.

Glycine nano-selenium prevents brain oxidative stress and neurobehavioral abnormalities caused by MPTP in rats.

BACKGROUND: Parkinson's disease (PD) is a common degenerative disease of the central nervous system in the elderly. In recent years, the results of clinical and experimental studies have shown that oxidative stress is one of the important pathogenesis of PD. Selenium is one of the minor elements reported to possess antioxidant properties. Thus, the purpose of this study was to investigate the recovery effect of glycine nano-selenium on neurobehavioral abnormalities and oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rat. MATERIALS AND METHODS: SD male rats weighing 280-310 g were purchased from the Chengdu Dossy Experimental Animals Company, China. All rats were housed in a temperature-controlled room, with a 12 h light-dark cycles and had free access to food and water ad libitum. Rats were randomly divided into 4 groups with 8 animals in each group: the control group (normal saline), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine group (MPTP), MPTP + 0.05 mg/kg glycine nano-selenium (MPTP + 0.05 Se), MPTP + 0.1 mg/kg glycine nano-selenium (MPTP + 0.1 Se). Behavioral assessment, clinical symptoms, Immunohistochemistry analysis of tyrosine hydroxylase (TH) and antioxidant activity were accessed to determine the protective effects glycine nano-selenium have on PD rats. RESULTS: From the results, Rats showed a decrease in spontaneous motor behavior and an increase in pole test score. Also, the number of TH+ neurons were also significantly decreased (P < 0.05) after treated with MPTP for 7 days indicating that MPTP could successfully induce neurobehavioral abnormalities in rats. Furthermore, the lipid peroxide (MDA) levels of the PD model group were significantly increased and the antioxidant activities (SOD and GSH-PX) were significantly inhibited (P < 0.05) compared to the control group indicating the important role oxidative stress played in dopaminergic neuron death and neurobehavioral abnormalities in PD rats. Compared with the PD model group, glycine nano-selenium administration could significantly improve behavior and increase the number of TH+ neurons (P < 0.05) to protect against the loss of dopaminergic neurons. At the same time, glycine nano-selenium could decrease the MDA levels and increase the activities of SOD and GSH-PX significantly (P < 0.05). CONCLUSION: In conclusion, PD rat model was successfully developed by intraperitoneal injection of MPTP and the intragastric administration of glycine nano-selenium reduced neurobehavioral abnormalities by decreasing oxidative stress in rat brain.

Soy isoflavones improve the oxidative stress induced hypothalamic inflammation and apoptosis in high fat diet-induced obese male mice through PGC1-alpha pathway.

Obesity is a common metabolic disorder that increases the risk of many diseases, such as type II diabetes, hypertension, cardiovascular disease. Hypothalamus plays a very important role in the progression of obesity, and many studies reveal that hypothalamic injures are implicated in obesity processes. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through improving the hypothalamic inflammation and apoptosis, which are induced by oxidative stress. Also, our in vitro studies demonstrate that daidzein and genistein, common ingredients of soy isoflavones, could protect hypothalamic N42 cells against palmitic acid induced oxidative stress and apoptosis. Moreover, the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1-alpha), which plays a role in oxidative defense, is increased after soy isoflavone treatment in vivo and in vitro, suggesting an improved effect of soy isoflavones on hypothalamic antioxidant defense is mediated by PGC-1α. Our study reveals a potential mechanism of soy isoflavones regulating oxidative stress induced hypothalamic inflammation and cellular apoptosis, which will be important for obesity treatment.

Iron overload resulting from the chronic oral administration of ferric citrate induces parkinsonism phenotypes in middle-aged mice.

Iron homeostasis is critical for maintaining normal brain physiological functions, and its mis-regulation can cause neurotoxicity and play a part in the development of many neurodegenerative disorders. The high incidence of iron deficiency makes iron supplementation a trend, and ferric citrate is a commonly used iron supplement. In this study, we found that the chronic oral administration of ferric citrate (2.5 mg/day and 10 mg/day) for 16 weeks selectively induced iron accumulation in the corpus striatum (CPu), substantia nigra (SN) and hippocampus, which typically caused parkinsonism phenotypes in middle-aged mice. Histopathological analysis showed that apoptosis- and oxidative stress-mediated neurodegeneration and dopaminergic neuronal loss occurred in the brain, and behavioral tests showed that defects in the locomotor and cognitive functions of these mice developed. Our research provides a new perspective for ferric citrate as a food additive or in clinical applications and suggests a new potential approach to develop animal models for Parkinson's disease (PD).

Soy Isoflavones Improve the Spermatogenic Defects in Diet-Induced Obesity Rats through Nrf2/HO-1 Pathway.

Soy isoflavones (SIF) are biologically active compounds of non-steroidal and phenolic properties that are richly present in soybeans, which can reduce the body weight and blood lipids of obese animals. Recently, SIF have been reported to affect reproductive ability in obese male rats. However, the specific mechanism has not been well defined. The aim of the current study was to study the possible mechanisms for the effect of SIF administration on obesity induced spermatogenic defects. Obese rats model induced by high-fat diets were established and gavage treated with 0, 50,150 or 450 mg of SIF/kg body weight/day for 4 weeks. Here, our research shows that obesity resulted in spermatogenic degeneration, imbalance of reproductive hormone, testicular oxidative stress and germ cell apoptosis, whereas evidently recovery effects were observed at 150 and 450 mg/kg SIF. We also have discovered that 150 and 450 mg/kg SIF can activate Nrf2/HO-1 pathway in control of Bcl-2, BAX and cleaved caspase-3 expression with implications in antioxidant protection. Our study indicates the potential mechanism of SIF regulating spermatogenic function in obese rats, and provides a scientific experimental basis for the regulation of biological function of obese male reproductive system by SIF.

Characterization of Inulin-Type Fructan from Platycodon grandiflorus and Study on Its Prebiotic and Immunomodulating Activity.

Platycodon grandiflorus is a plant widely used in traditional Chinese medicine, of which polysaccharides are reported to be the main components responsible for its bio-functions. In this work, the inulin-type fructan (PGF) was obtained by DEAE anion exchange chromatography from the water extracted from P. grandifloras. Characterization was performed with methanolysis, methylation, and NMR and the results showed that PGF is a ß-(2-1) linked fructan, with terminal glucose and with a degree of polymerization of 2⁻10. In order to study its biofunctions, the prebiotic and immunomodulation properties were assayed. We found that PGF exhibited good prebiotic activity, as shown by a promotion on six strains of lactobacillus proliferation. Additionally, the PGF also displayed direct immunomodulation on intestinal epithelial cells and stimulated the expressions of anti-inflammatory factors. These results indicated that the inulin from P. grandiflorus is a potential natural source of prebiotics as well as a potential intestinal immunomodulator, which will be valuable for further studies and new applications.

Improvement of Colonic Immune Function with Soy Isoflavones in High-Fat Diet-Induced Obese Rats.

Background: The damage to intestinal barrier function plays an important role in the development of obesity and associated diseases. Soy isoflavones are effective natural active components for controlling obesity and reducing the level of blood lipid. Here, we explored whether these effects of soy isoflavones were associated with the intestinal barrier function. Methods and Results: The obese rat models were established by high fat diet feeding. Then, those obese rats were supplemented with soy isoflavones at different doses for 4 weeks. Our results showed that obesity induced the expressions of pro-inflammatory cytokines, decreased the anti-inflammatory cytokine (IL-10) expression, elevated intestinal permeability, altered gut microbiota and exacerbated oxidative damages in colon. The administration of soy isoflavones reversed these changes in obese rats, presenting as the improvement of intestinal immune function and permeability, attenuation of oxidative damage, increase in the fraction of beneficial bacteria producing short-chain fatty acids and short-chain fatty acid production, and reduction in harmful bacteria. Furthermore, soy isoflavones blocked the expressions of TLR4 and NF-κB in the colons of the obese rats. Conclusions: Soy isoflavones could improve obesity through the attenuation of intestinal oxidative stress, recovery of immune and mucosal barrier, as well as re-balance of intestinal gut microbiota.

A pectic polysaccharide from water decoction of Xinjiang Lycium barbarum fruit protects against intestinal endoplasmic reticulum stress.

Neutral polysaccharides from Ningxia L. barbarum fruit have been reported with immunomodulatory and antioxidative biological activities. Few studies on pectic polysaccharides have been reported, especially not from the Xinjiang L. barbarum. In the present study, a pectic polysaccharide, XLBP-I-I, was obtained from water decoction of Xinjiang L. barbarum using anion exchange chromatography and gel filtration. The results from methanolysis, methylation, FT-IR and NMR experiments indicated that XLBP-I-I was a typical pectic polysaccharide. In vitro assay showed that XLBP-I-I could reduce the ER stress and UPR in tunicamycin insult IPEC-J2 cells, and further protect IPEC-J2 cells against apoptosis induced by ER stress. These results reveal a new perspective for pectic L. barbarum polysaccharides on intestine ER stress, and this elicited interests for its further applications.

Selenium Ameliorates AFB1-Induced Excess Apoptosis in Chicken Splenocytes Through Death Receptor and Endoplasmic Reticulum Pathways.

Aflatoxin B1 (AFB1) can cause hepatotoxicity, genotoxicity, and immunosuppressive effects for a variety of organisms. Selenium (Se), as an essential nutrient element, plays important protective effects against cell apoptosis induced by AFB1. This research aimed to reveal the ameliorative effects of selenium on AFB1-induced excess apoptosis in chicken splenocytes through death receptor and endoplasmic reticulum pathways in vivo. Two hundred sixteen neonatal chickens, randomized into four treatments, were fed with basal diet (control treatment), 0.4 mg/kg Se supplement (+Se treatment), 0.6 mg/kg AFB1 (AFB1 treatment), and 0.6 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 + Se treatment) during 21 days of experiment, respectively. Compared with the AFB1 treatment, the levels of splenocyte apoptosis in the AFB1 + Se treatment were obviously dropped by flow cytometry and TUNEL assays although they were still significantly higher than those in the control or + Se treatments. Furthermore, the mRNA expressions of CASP-3, CASP-8 and CASP-10, GRP78, GRP94, TNF-α, TNF-R1, FAS, and FASL of splenocytes in the AFB1 + Se treatment by qRT-PCR assay were significantly decreased compared with the AFB1 treatment. These results indicate that Se could partially ameliorate the AFB1-caused excessive apoptosis of chicken splenocytes through downregulation of endoplasmic reticulum and death receptor pathway molecules. This research may rich the knowledge of the detoxification mechanism of Se on AFB1-induced apoptosis.

Ameliorative effects of selenium on the excess apoptosis of the jejunum caused by AFB1 through death receptor and endoplasmic reticulum pathways.

Aflatoxin B1 (AFB1), one of most potent and common mycotoxins in human food and animal feed, has hepatotoxic and carcinogenic effects on humans and poultry. Recent studies indicated that selenium (Se) has a protective effect on apoptosis induced by toxin poisoning. The present study was designed to reveal the ameliorative effects of selenium on the expression of apoptosis related molecules in the jejunum of broilers exposed to an AFB1 diet for 3 weeks. A total of 216 one-day-old healthy Cobb broilers were randomly divided into the control group (0 mg kg-1 AFB1), AFB1 group (0.6 mg kg-1 AFB1), AFB1 + Se group (0.6 mg kg-1 AFB1 + 0.4 mg kg-1 supplement Se) and Se group (0.4 mg kg-1 supplement Se), respectively. TUNEL and flow cytometry assays both indicated that 0.4 mg kg-1 selenium could ameliorate excess apoptosis caused by AFB1 in jejunal cells. Moreover, the expressions of FAS, FASL, TNF-α, TNF-R1, CASPASE-3, CASPASE-8, CASPASE-10, GRP78 and GRP94 analyzed by qRT-PCR demonstrated that 0.4 mg kg-1 selenium restored these parameters to be close to those in the control group. In summary, supplementation of selenium at a concentration of 0.4 mg kg-1 selenium could protect the chicken's jejunum from excess apoptosis caused by 0.6 mg kg-1 AFB1 through down-regulating the expression of death receptor pathway and endoplasmic reticulum pathway related molecules. According to this conclusion, this study may contribute to a better understanding of selenium's protective role against AFB1 poisoning.

Endocannabinoid hydrolase and cannabinoid receptor 1 are involved in the regulation of hypothalamus-pituitary-adrenal axis in type 2 diabetes.

Hypothalamus-pituitary-adrenal (HPA) axis, as the key moderator in energy metabolism, plays an important role in diabetes. The endogenous cannabinoid system (eCBs) involves in neuronal functions, and simultaneously cannabinoid receptors are almost expressed in all regions of the hypothalamus according to a spate of reports. However, few data investigate the changes of eCBs and HPA axis in type 2 diabetes. In this study, five diabetes mellitus rhesus monkeys, five prediabetes rhesus monkeys and five healthy rhesus monkeys were observed. In the present study, we detected cell swelling and necrosis extensively in the paraventricular nucleus (PVN) and neurohypophysis in prediabetes and overt diabetes monkeys. The adrenocorticotropic hormone in the pituitary gland, adrenocorticotropic hormone receptor, and 11ß-hydroxysteroid dehydrogenase in the adrenal gland were all hyper-secreted and expressed from healthy to overt diabetes. Meanwhile, the cortisol concentration in the adrenal gland was increased along with the progress of diabetes. It could be concluded that hyperfunction of the HPA axis exists in the type 2 Diabetes pathogenesis. However, we also found a weakened expression and secretion of corticotrophin releasing hormone and glucocorticoids receptor in PVN. The expression of corticotropin releasing hormone receptor 1 in pituitary gland decreased in prediabetes monkeys, but increased in overt diabetes monkeys. The downregulation of cannabinoid receptor 1 and upregulation of monoglycerol lipase and fatty acid amide hydrolase in PVN was involved in the pathogenesis of type 2 diabetes. Collectively, we can conclude that changes in endocannabinoid hydrolase and cannabinoid receptor might indicate the effect of downregulation of eCBs. It can be assumed that hyper-function of the HPA axis from healthy to overt diabetes is due to the undermining inhibition of eCBs. However, the regulatory mechanism of eCBs targets on the HPA axis need to be further explored.

The molecular mechanism of cell cycle arrest in the Bursa of Fabricius in chick exposed to Aflatoxin B 1.

Aflatoxin B1 shows potent hepatotoxic, carcinogenic, genotoxic, immunotoxic potential in humans and many species of animals. The aim of this study was to clarify the underlying mechanism of G0G1 phase and G2M phase arrest of cell cycle in the bursa of Fabricius in broilers exposed to dietary AFB1. 144 one-day-old healthy Cobb broilers were randomly divided into two groups and fed on control diet and 0.6 mg·Kg-1 AFB1 diet for 3 weeks. Histological observation showed that AFB1 induced the increase of nuclear debris and vacuoles in lymphoid follicle of BF. Results of flow cytometry studies showed that bursal cells arrested in G2M phase at 7 days of age and blocked in G0G1 phase at 14 and 21 days of age following exposure to AFB1. The qRT-PCR analysis indicated that cell cycle arrested in G2M phase via ATM-Chk2-cdc25-cyclin B/cdc2 pathway, and blocked in G0G1 phase through ATM-Chk2-cdc25-cyclin D/CDK6 pathway and ATM-Chk2-p21-cyclin D/CDK6 route. In a word, our results provided new insights that AFB1 diet induced G2M and G0G1 phase blockage of BF cells in different periods, and different pathways were activated in different arrested cell cycle phase.

Effects of dietary vitamin E on growth performance as well as intestinal structure and function of channel catfish (Ictalurus punctatus, Rafinesque 1818).

To evaluate the impact of dietary vitamin E supplementation on growth performance, the intestinal structure and function of channel catfish (Ictalurus punctatus, Rafinesque 1818) was investigated. A total of 900 healthy channel catfish (weight, 5.20±0.15 g) were divided into four groups, which received experimental diets with different vitamin E content (0, 50, 100 or 1,000 mg/kg). At the end of the feeding trial (after 15 weeks), the growth and gut performance of the animals was determined. The digestive enzyme activity in hepatopancreas and gut was also detected. In addition, the height of intestinal fold, the thickness of the mucous membrane and the number of somatostatin-positive cells was examined by histological analysis. Dietary vitamin E supplementation at 50 and 100 mg/kg significantly improved the growth and gut performance, which also increased the activity of several digestive enzymes compared to that in animals without vitamin E supplementation (P<0.05). In addition, vitamin E supplementation also significantly increased the height of intestinal fold and the thickness of the mucous membrane (P<0.05). Fish with dietary vitamin E supplementation at appropriate doses also had more somatostatin-positive cells in than those without vitamin E supplementation (P<0.05). In conclusion, dietary vitamin E supplementation at 50 and 100 mg/kg was shown to improve the growth performance as well as intestinal structure and function of channel catfish.