Tumor Necrosis Factor-α Gene Research Articles

Mechanism of Biejiajian Pills against non-alcoholic steatohepatitis based on lipidomics

This study aims to explore the potential mechanism of Biejiajian Pills in the treatment of non-alcoholic steatohepatitis(NASH) based on lipidomics. A mouse model of NASH was induced by high-fat/high cholesterol diet, and the mice of the normal group were fed with a normal diet. The therapeutic efficacy of Biejiajian Pills against NASH was evaluated through biochemical indexes in both of serum and liver, as well as the hepatic histopathology. Lipid metabolites in the liver were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)-based lipidomics. Then the partial least-squares discriminant analysis, t-test and receiver operating characteristic curve analysis were performed to screen the differential lipid metabolites and the main biomarkers. The proteins and genes involved in the lipid metabolism and inflammatory response were detected by Western blot and qPCR. The results demonstrated that Biejiajian Pills notably lowered the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the serum and the levels of triglyceride(TG) and total cholesterol(TC) in the liver tissue. In addition, Biejiajian Pills alleviated the lipid accumulation, hepatocyte ballooning, and liver fibrosis. Lipidomics revealed that Biejiajian Pills regulated the content of 11 biomarkers including phosphatidyl choline(PC), phosphatidyl ethanolamine(PE), sphingomyelin(SM), and ceramide(Cer). The results of Western blot and qPCR demonstrated that Biejiajian Pills regulated the expression of sterol regulatory element-binding protein 1(SREBP1), peroxisome proliferator-activated receptor gamma(PPARγ) and phospho-AMP-activated protein kinase(p-AMPK), and the mRNA level of fatty acid translocase 36 gene(Cd36), Pparγ, cardiolipin synthase 1 gene(Crls1), and phospholipase Cβ2 gene(Plcβ2). Furthermore, Biejiajian Pills displayed inhibitory effects on phospho-p38 MAPK(p-p38 MAPK) and phospho-ERK1/2(p-ERK1/2) and the mRNA levels of interleukin-6 gene(Il-6), interleukin-1β gene(Il-1β) and tumor necrosis factor-α gene(Tnf-α). In conclusion, Biejiajian Pills could alleviate the lipid metabolism disorders and regulate the expression of SREBP1, PPARγ, and p-AMPK and the mRNA levels of pro-inflammatory cytokines.

Ameliorative Effect of Macadamia Nut Protein Peptides on Acetaminophen-Induced Acute Liver Injury in Mice.

This study aims to examine the ameliorative effect of macadamia nut protein peptides (MPP) on acetaminophen (APAP)-induced liver injury (AILI) in mice, and develop a new strategy for identifying hepatoprotective functional foods. The molecular weight distribution and amino acid composition of MPP were first studied. Forty mice were then randomized into four groups: control group (CON), APAP model group, APAP+MPP low-dose group (APAP+L-MPP), and APAP+MPP high-dose group (APAP+H-MPP). The APAP+L-MPP (320 mg/kg per day) and APAP+H-MPP (640 mg/kg per day) groups received continuous MPP gavage for 2 weeks. A 12 h of APAP (200 mg/kg) gavage resulted in liver damage. Pathological alterations, antioxidant index levels, expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB), and associated inflammatory factors were determined for each treatment group. The results revealed that the total amino acid content of MPP was 39.58 g/100 g, with Glu, Arg, Asp, Leu, Tyr, and Gly being the major amino acids. The molecular weight range of 0-1000 Da accounted for 73.54%, and 0-500 Da accounted for 62.84% of MPP. MPP ameliorated the pathological morphology and reduced the serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase of AILI in mice. MPP significantly increased the activities of superoxide dismutase and glutathione peroxidase in the liver compared with the APAP group. MPP inhibited the expression of TLR4, NF-κB, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) genes in AILI mice. MPP also inhibited the expression levels of inflammatory factors (TNF-α and IL-6). Our study concludes that MPP alleviates AILI in mice by enhancing antioxidant capacity and inhibiting TLR4/NF-κB pathway-related gene activation.

Potential Benefits of Integrin αvβ3 Antagonists in a Mouse Model of Experimental Dry Eye.

The purpose of this study was to extensively evaluate the efficacy of integrin αvβ3 antagonists for the treatment of experimental dry eye (EDE). Vitronectin, an αvβ3 ligand, was used to induce tumor necrosis factor-α gene expression in human THP-1 macrophages. To induce EDE, C57BL/6 mice were housed in a low-humidity controlled environment chamber and injected subcutaneously with scopolamine for 7 days. Subsequently, αvβ3 antagonists, including RGDfD, c(RGDfD), c(RGDiD), c(RGDfK), ATN-161, SB273005, and cilengitide, were administered topically to EDE animals under controlled environment chamber conditions. Corneal epithelial damage in EDE was assessed by fluorescein staining. The density of conjunctival goblet cells and secretion of tears was measured by period acid-Schiff staining and phenol red-impregnated cotton threads, respectively. Inflammation markers, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17A, and metalloproteinase (MMP)-9, in the pooled cornea and conjunctiva tissues were examined by real-time polymerase chain reaction. The inhibitory effects of αvβ3 antagonists on the vitronectin-induced tumor necrosis factor-α gene expression and integrin-mediated inflammatory signaling were validated in THP-1 macrophages. αvβ3 antagonists ameliorated the impairment of the corneal epithelial barrier with varying therapeutic efficacies, compared with vehicle-treated mice. c(RGDfD) and c(RGDiD) significantly protected against goblet cell loss, tear reduction, and proinflammatory gene expression in EDE. Topical applications of αvβ3 antagonists yield therapeutic benefits in EDE by promoting corneal epithelial defect healing and reducing inflammation. Antagonistic targeting αvβ3 may be a novel promising strategy to treat patients with dry eye disease.

Copper Super-Dosing Improves Performance of Heat-Stressed Broiler Chickens through Modulation of Expression of Proinflammatory Cytokine Genes.

Continuous exposure to high ambient temperatures brings about a number of oxidative damages in chickens. Copper (Cu), an active component of a number of antioxidative defence components, should arrest these changes to take place although that may not be possible under the standard dosing regimen followed by the industry. To ascertain the optimum dose response that may be beneficial in sustaining the performance of chickens under heat stress (HS), broiler chickens (n = 400) were exposed to high ambient temperature (between 27.2°C and 35.3°C) during 1-35 d. Copper (Cu) as Cu proteinate (Cu-P) at concentrations of 37.5, 75, 112.5, and 150 mg/kg was supplemented to the diet. The negative control (NC) diet did not contain any supplemental Cu. Increasing dietary Cu improved (P < 0.001) body weight, feed intake, and conversion ratio. Serum concentrations of total cholesterol at 21 d (P = 0.009), HDL cholesterol at 35 d (P = 0.008), LDL cholesterol at 21 d (P = 0.015), and triacylglycerol at both 21 d (P = 0.033) and 35 d (P = 0.001) decreased as Cu in the diet increased. As Cu in the diet increased, hemoglobin increased (P = 0.003) at 21 d, and the heterophil to lymphocyte ratio decreased both at 21 d (P = 0.047) and 35 d (P = 0.001). Superoxide dismutase and glutathione peroxidase activities increased when dietary Cu increased to 150 mg/kg (P < 0.01). Liver Cu at 35 d increased linearly with the dose of Cu in the diet (P = 0.0001). Selected bacteria were enumerated in the digesta to ascertain if Cu super-dosing affected their population in any way in the absence of any enteric challenge. Escherichia coli and total Salmonella numbers decreased (P = 0.0001), and total Lactobacillus increased (P = 0.0001) proportionately with dietary Cu. Interleukin-6 and tumour necrosis factor-α gene expression increased linearly (P = 0.0001) as Cu in the diet increased though the response plateaued at 112.5 mg/kg. It was concluded from the present experiment that during conditions of impending HS, dietary supplementation of 112.5 to 150 mg Cu/kg diet as Cu-P may be a novel strategy to alleviate the negative effects of HS without involving any apparent risk of Cu toxicity.

Tumor Necrosis Factor-α (-308G>A) Gene Polymorphism and Its Association with Asthma and Atopy Status.

Asthma is one of the most prevalent chronic lung diseases that afflict genetically predisposed individuals. Certain cytokine gene polymorphisms have been associated with asthma. Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine that can modulate nonspecific inflammation to influence asthma. This study aimed to define the relationship between the TNF gene polymorphism at position -308 and asthma susceptibility, as well as atopic and non-atopic asthma. Using polymerase chain reaction with sequence-specific primers, we investigated genotype frequencies and alleles of a polymorphic gene coding for TNF-α in 86 pediatric patients with asthma and 470 healthy controls of the same race. Seventy-four patients underwent a skin prick test. The homozygous AA variant (-308, rs1800629) was the most common genotype among patients, accounting for 63.3% of all cases. In contrast, homozygous GG (-308) was significantly less prevalent in the patient group compared to the control group. TNF A (-308) allele frequency was 85.5% among asthma patients and 16.6% among healthy controls. The genotype and allele frequencies of TNF (-308 A>G, rs1800629) did not differ between atopic and non-atopic asthma. In conclusion, TNF (-308) AA and AG genotypes are associated with asthma susceptibility in Iranian children, although there was no significant difference in polymorphism between atopic and non-atopic asthma and no difference in asthma severity groups.

TNF-α -308A/G SNP association with kidney allograft rejection in Algerian population: A retrospective case-control study

No consensus has been reached regarding the association beween the -308A/G single nucleotide polymorphism (SNP) in the tumor necrosis factor-α gene (TNFA) and kidney allograft rejection (KAR). Our retrospective case-control study aimed to assess the association of the SNP with KAR in Algerian patients who underwent kidney transplantation. The study enrolled 313 Algerian patients: 58 kidney-transplant recipients without rejection events (PWoR); 58 kidney-transplant recipients with at least one rejection event, with or without graft loss (PWR); and 197 healthy individuals (HI). The TNFA -308A/G SNP was genotyped using a real-time polymerase chain reaction. The results demonstrated that, the frequencies of TNFA -308A allele and AA genotype were higher in the PWR than in the HI groups (p = 0.001, OR = 2.26, CI = 1.33‐3.77 and p = 0.0004, OR = 5.53, CI-1.89-16.6, respectively). Furthermore, the frequencies were higher among the PWR than among the PWoR groups (p = 0.001, OR = 3.29, CI = 1.56‐7.21 and p = 0.0006, OR = 28.26, CI = 1.62‐493.2, respectively), particularly among PWR patients with de novo anti-human leukocyte antigens (HLA) antibodies (PG-a-HLA-Ab). However, the frequency of TNFA -308G allele was lower in the PWR group than in the PWoR group (p = 0.001, OR = 0.3, CI = 0.1‐0.64) and the HI group (p = 0.001, OR = 0.44, CI = 0.27‐0.44). Our results suggest an association of the TNFA -308A/G alleles with KAR in Algerian patients who underwent kidney transplantation. Carriers of TNFA -308A allele who have PG-a-HLA-Ab might have a higher risk, whereas TNFA -308G allele carriers could have a lower risk of KAR. Thus, therapeutic strategies can be adapted to minimize KAR risk in patients who have a genetic proclivity for increased pro-inflammatory TNF-α activity.

Host–pathogen interaction unveiled by immune, oxidative stress, and cytokine expression analysis to experimental Saprolegnia parasitica infection in Nile tilapia

The present study evaluated the pathogenicity, immunological, and oxidant/antioxidant responses against Saprolegnia parasitica (S. parasitica) infection in Nile tilapia (Oreochromis niloticus). Three groups of Nile tilapia were assigned as the control group (no zoospores exposure). The other two groups were challenged by Saprolegnia zoospores; one was used for sampling, and the other for mortality monitoring. The study lasted 3 weeks and was sampled at three point times at 1, 2, and 3 weeks. Results showed that S. parasitica zoospores were pathogenic to Nile tilapia, causing a cumulative mortality rate of 86.6%. Immunoglobulin M and C- reactive protein (IgM and CRP) levels showed a similar trend being significantly (P < 0.05, P < 0.001) higher in the infected group at weeks 1, 2, and 3, respectively, compared to the control group. Oxidant and antioxidant parameters in gills revealed that Malondialdehyde (MDA) level was significantly higher in the infected group compared to the control group. While catalase, glutathione peroxidase, and superoxide dismutase (CAT, GSH, and SOD) levels were significantly decreased in the infected group compared to the control group. Compared to the control, the tumor necrosis factor-α (TNF-α) gene was firmly upregulated in gill tissue at all-time points, particularly at day 14 post-infection. Meanwhile, Interleukin 1-β (IL-1 β) gene was significantly upregulated only at days 7 and 14 post-infection compared to control. Histopathological examination revealed destructive and degenerative changes in both skin and gills of experimentally infected Nile tilapia. Our findings suggest that Nile tilapia-S. parasitica infection model was successful in better understanding of pathogenicity and host (fish)-pathogen (oomycete) interactions, where the induced oxidative stress and upregulation of particular immune biomarkers in response to S. parasitica infection may play a crucial role in fish defense against oomycetes in fish.

The Effects of Grapevine (Vitis vinifera L.) Leaf Extract on Growth Performance, Antioxidant Status, and Immunity of Zebrafish (Danio rerio)

An 8-week feeding trial was carried out to evaluate the effects of grapevine (Vitis vinifera) leaf extract (GLE) on the growth, oxidative enzymatic activities, immunity, and expression of antioxidant genes in zebrafish (Danio rerio). Three hundred and sixty zebrafish were supplied and fed with different levels of GLE: 0, 0.5, 1, and 2 g kg−1. The dietary administration of 1 g kg−1 of GLE significantly increased growth parameters in fish. Fish fed diets with GLE showed increased total protein. The total Ig and lysozyme activity significantly changed in the whole-body serum, but not in skin mucus. GLE significantly increased Catalase (CAT), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) activities compared to the control diet. GLE treatments caused a significant decrease in the malondialdehyde (MDA) content. In the skin mucus, only CAT and SOD activities significantly increased. The highest expression of Toll-like receptor-1 (TLR-1) and Tumor Necrosis Factor-α (TNFα) genes was achieved in fish fed 2 g kg−1 of GLE. CAT and SOD gene expressions were significantly higher in fish fed 1 and 2 g kg−1 of GLE. GPx gene expression was significantly higher in fish fed 1 g kg−1 of GLE. In conclusion, the results of the present study revealed that GLE affects growth performance and regulates antioxidant and immune gene expression. The determination of the optimum dosage merits further research.

Norcantharidin potentiates sorafenib antitumor activity in hepatocellular carcinoma rat model through inhibiting IL-6/STAT3 pathway

In hepatocellular carcinoma (HCC), sorafenib (Sora) efficacy is limited by primary and/or acquired resistance. Emerging evidence shows that the inflammatory factor interleukin 6 (IL-6) plays a role in Sora resistance. Norcantharidin (NCTD), a derivative of cantharidine, was identified as a potent IL-6 inhibitor. Thus, in this study, we evaluated NCTD ability to improve the Sora efficacy in HCC and its underlying molecular mechanisms. Male Sprague Dawely rats were administered NCTD (0.1 mg/kg/day; orally) or Sora (10 mg/kg day; orally) or combination for 6 weeks after HCC induction using thioacetamide (200 mg/kg; ip; 2 times/wk) for 16 weeks. Our results showed that NCTD greatly enhanced Sora activity against HCC and potentiated Sora-induced oxidative stress. NCTD enhanced Sora-induced tumor immunity reactivation by decreasing both fibrinogen-like protein 1 level and increasing both tumor necrosis factor-α gene expression along with CD8+ T cells number. Also, NCTD augmented Sora attenuation activity against TAA-induced angiogenesis and metastasis by decreasing VEGFA, HIF-1α, serum lactate dehydrogenase enzyme, and vimentin levels. The combined use of NCTD/Sora suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, neurogenic locus notch homolog protein, spalt-like transcription factor 4, and CD133. NCTD boosted Sora antiproliferative and apoptotic activities by decreasing Ccnd1 and BCL2 expressions along with increasing BAX and caspase-3 expressions. To our knowledge, this study represents the first study providing evidence for the potential novel therapeutic use of NCTD/Sora combination for HCC. Moreover, no previous studies have reported the effect of NCTD on FGL1.

Association of genetic variation in tumor necrosis factor-α gene with susceptibility to rheumatoid arthritis in southern Iraq

: Rheumatoid arthritis is the most commonly occurring systemic autoimmune disease caused by genetic, epigenetic, and environmental factors. It affects 0.5-1% of the worldwide population and increases in incidence with age. Tumor necrosis factor-α, major candidate gene in the pathogenesis of RA. Gene polymorphisms occurring in this pro-inflammatory cytokine may increase the risk of RA. This study aimed to evaluate the association between polymorphisms in TNF-α gene at location -308(rs1800629), -238(rs361525) and -376(1800750) (G/A) and RA susceptibility. The study also evaluated the effects of these polymorphisms on their corresponding gene levels in serum. Methods: This case-control study was conducted on 49 individuals (30 RA patients and 19 age- and sex-matched healthy volunteers as controls). Genomic DNA extracted from all participant blood, then amplified by PCR and genotyped by sequencing.Additionally, the serum level of TNF-α was quantified using an enzyme-linked immunosorbent assay (ELISA). Results: The results showed that thehomozygosity for the TNF-α -308 G allele significantly act as a genetic factor associated with increased RA risk (p = 0.029, OR: 4.727, 95%CI: 1.175–19.016). The A allele of -238 and -376 polymorphisms may act as a possible risk factor for RA (OR: 7.63, 95%CI:0.409-14.07; OR:6.13, 95%CI:.0.32-11.214). However, no significant differences were observed. Conclusion: The GG genotype ofTNF-α -308 SNP associated with increased rheumatoid arthritis risk.

Effects of Dietary Steroid Saponins on Growth Performance, Serum and Liver Glucose, Lipid Metabolism and Immune Molecules of Hybrid Groupers (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatu) Fed High-Lipid Diets.

High-lipid diets are attributed to excessive lipid deposition and metabolic disturbances in fish. The aim of this experiment was to investigate the effects of steroidal saponins on growth performance, immune molecules and metabolism of glucose and lipids in hybrid groupers (initial weight 22.71 ± 0.12 g) fed high-lipid diets. steroidal saponins (0%, 0.1% and 0.2%) were added to the basal diet (crude lipid, 14%) to produce three experimental diets, designated S0, S0.1 and S0.2, respectively. After an 8-week feeding trial, no significant differences were found between the S0 and S0.1 groups in percent weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio and protein deposition rate (p > 0.05). All those in the S0.2 group were significantly decreased (p < 0.05). Compared to the S0 group, fish in the S0.1 group had lower contents of serum triglyceride and low-density lipoprotein cholesterol and higher high-density lipoprotein cholesterol and glucose (p < 0.05). The activities of superoxide dismutase, catalase and glutathione peroxidase were significantly higher, and malondialdehyde contents were significantly lower in the S0.1 group than in the S0 group (p < 0.05). Hepatic triglyceride, total cholesterol and glycogen were significantly lower in the S0.1 group than in the S0 group (p < 0.05). Activities of lipoprotein lipase, total lipase, glucokinase and pyruvate kinase, and gene expression of lipoprotein lipase, triglyceride lipase and glucokinase, were significantly higher in the S0.1 group than in the S0 group. Interleukin-10 mRNA expression in the S0.1 group was significantly higher than that in the S0 group, while the expression of interleukin-6 and tumor necrosis factor-α genes were significantly lower than those in the S0 group. In summary, adding 0.1% steroidal saponins to a high-lipid diet not only promoted lipolysis in fish livers, but also activated glycolysis pathways, thus enhancing the utilization of the dietary energy of the groupers, as well as supporting the fish's nonspecial immune-defense mechanism.

PS-B05-4: COMPARATIVE EFFECTS OF RENAL DENERVATION IN DIFFERENT STAGES OF HYPERTENSION ON CARDIAC, RENAL, AND ADIPOSE PATHOLOGY IN DAHL SALT-SENSITIVE RATS

Objective: Renal denervation (RDN) has emerged as a novel therapy for resistant hypertension. In Dahl salt-sensitive (DahlS) rats, RDN does not prevent the development of hypertension but attenuates the progression of hypertension. We have now investigated the comparative effects of RDN in early versus advanced stages of hypertension on cardiac, renal, and adipose tissue pathology in DahlS rats. Design and method: Male DahlS rats fed an 8% NaCl diet after 6 weeks of age were subjected to RDN or sham surgery at 7 (early stage) or 9 (advanced stage) weeks. In the RDN groups, all visible nerves along the vessels were cut and the vessels were painted with a solution of 10% phenol in absolute ethanol. In contrast, in the sham-operated groups, the kidneys were exposed but the vessels were not stripped or coated with phenol. At 12 weeks, left ventricular (LV), renal, and adipose tissue were excised for analysis. Results: Successful RDN was confirmed by determination of renal norepinephrine content in each rat subjected to RDN less than 10% of the mean values of those in the sham-operated groups. Although both stages of RDN modestly attenuated blood pressure elevation, they improved LV diastolic function and fibrosis and attenuated macrophage infiltration and expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) genes in the heart, to a similar extent. In addition, both stages of RDN similarly reduced macrophage infiltration in glomeruli, the glomerulosclerosis index, the tubulointerstitial injury score as well as expression of MCP-1 and TNF-α genes in the kidney. The early stage group showed reductions in both retroperitoneal fat mass and adipocyte cross-sectional area, whereas the advanced stage group did an increase in fat mass without any change in adipocyte size. Conclusions: Both early and advanced stages of RDN mildly attenuated hypertension as well as ameliorated cardiac and renal injury, to a similar extent, in salt-loaded DahlS rats. The anti-hypertensive effect of RDN is thus likely attributable primarily to improved renal pathology. These results also suggest a possible crosstalk among the kidney, cardiovascular system, and adipose tissue via neural mechanisms in salt-sensitive hypertension.

In vitro and in vivo evaluation of the antiviral activity of arctigenin, ribavirin, and ivermectin against viral hemorrhagic septicemia virus infection

Viral hemorrhagic septicemia virus (VHSV) causes a severe and often lethal infection in olive flounder (Paralichthys olivaceus) in Korea, resulting in mass mortality and substantial economic loss. As a potential prevention strategy for infectious viral diseases, this study aimed to evaluate the antiviral activity of three compounds (arctigenin [ARG], ribavirin [RBV], and ivermectin [IVM]) against VHSV infection in vitro and in vivo. In epithelioma papulosum cyprini cells, the expression of both VHSV glycoprotein (G) and nucleoprotein (N) genes were significantly suppressed by the three compounds in a dose-dependent manner (P < 0.05). Also, cell morphology and viability were maintained at the following concentrations: ARG 1.5 mg/L, RBV 2.5 mg/L, and IVM 10 mg/L. The fish that were treated with RBV (8.33 mg/kg) and IVM (0.25 mg/kg) before VHSV infection and those treated with IVM (0.25 mg/kg) after VHSV infection showed significant improvements in the survival rate, a reduction in the viral shedding rate, and downregulation of viral gene expression compared to those seen in fish with naïve VHSV infections. Furthermore, among the innate immune genes studied, persistent expression of Mx and upregulation of tumor necrosis factor-α gene expression in VHSV-infected fish treated with RBV and IVM revealed that these compounds might induce an immunostimulatory effect as one of their antiviral activities. Overall, this study supports the use of RBV and IVM as antiviral agents to control VHSV infections in olive flounder.

Effects of Yeast Culture Supplementation on Growth Performance, Nutrient Digestibility, Blood Metabolites, and Immune Response in Geese.

Simple SummaryAntibiotics benefit animal growth performance and health. However, an overuse of antibiotics can lead to antibiotic residue and the development of drug-resistant bacteria. Considering the possible serious consequences of antibiotic overuse, non-antibiotic alternatives, such as yeast and yeast products, are widely used in animal diets to improve growth and productive performance. Geese are important poultry, and their meat provides high-quality protein to humans, but studies showing how yeast culture affect geese are limited. On this basis, the effects of dietary yeast culture supplementation on growth performance, nutrient digestibility, blood metabolites, and immune functions of geese were studies. The results showed that the dietary addition of yeast culture could improve growth performance and nutrient digestibility and can modulate the immune response of geese. This dietary strategy based on feed additives is an effective method for improving the growth efficiency of the geese.The present study was conducted to investigate the effects of dietary yeast culture (YC) supplementation on growth performance, nutrient digestibility, blood metabolites, and immune functions in geese. One-day-old Sichuan white geese (n = 300) were randomly divided into five groups containing 0 (control), 0.5%, 1.0%, 2.0%, and 4.0% of YC in the diet for 70 days. In general, the dietary supplementation of YC significantly increased the average daily gain and feed conversion ratio (p < 0.05) in which the 1.0% or 2.0% levels were better and significantly reduced the average daily feed intake at the 2.0% level (p < 0.05). YC supplementation increased digestibility of P (quadratic, p = 0.01) and gross energy (quadratic, p = 0.04) from days 23 to 27 and crude protein from days 23 to 27 and days 64 to 68 (quadratic, p ≤ 0.05), with the 2.0% level being the most effective. Serum metabolites were significantly affected by dietary YC (p < 0.05). Supplemental YC increased IL-2 on day 28 (linear, p = 0.01; quadratic, p = 0.04) and lysozyme on day 70 (quadratic, p = 0.04) and decreased complement C4 on day 70 (linear, p = 0.05). Interferon-γ, interleukin-2, and tumor necrosis factor-α genes were mostly up-regulated after YC supplementation, and interferon-γ and interleukin-2 gene expression levels were significantly increased at the 2.0% level (p < 0.05). Taken together, dietary YC supplementation improved growth performance and affected nutrient digestibility, serum metabolites, and immune function in geese, which was optimized at the 2% YC level in the present study.

Consumption of Yeast-Fermented Wheat and Rye Breads Increases Colitis and Mortality in a Mouse Model of Colitis

BackgroundCereals are known to trigger for wheat allergy, celiac disease and non-celiac wheat sensitivity (NCWS). Inflammatory processes and intestinal barrier impairment are suspected to be involved in NCWS, although the molecular triggers are unclear.AimsWe were interested if different bread types influence inflammatory processes and intestinal barrier function in a mouse model of inflammatory bowel disease.MethodsEpithelial caspase-8 gene knockout (Casp8ΔIEC) and control (Casp8fl) mice were randomized to eight groups, respectively. The groups received different diets for 28 days (gluten-free diet, gluten-rich diet 5 g%, or different types of bread at 50 g%). Breads varied regarding grain, milling and fermentation. All diets were isocaloric.ResultsRegardless of the diet, Casp8ΔIEC mice showed pronounced inflammation in colon compared to ileum, whereas Casp8fl mice were hardly inflamed. Casp8fl mice could tolerate all bread types. Especially yeast fermented rye and wheat bread from superfine flour but not pure gluten challenge increased colitis and mortality in Casp8ΔIEC mice. Hepatic expression of lipopolysaccharide-binding protein and colonic expression of tumor necrosis factor-α genes were inversely related to survival. The bread diets, but not the gluten-rich diet, also decreased colonic tight junction expression to variable degrees, without clear association to survival and inflammation.ConclusionsBread components, especially those from yeast-fermented breads from wheat and rye, increase colitis and mortality in Casp8ΔIEC mice highly susceptible to intestinal inflammation, whereas control mice can tolerate all types of bread without inflammation. Yet unidentified bread components other than gluten seem to play the major role.

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes.

IntroductionKidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved over the past two decades. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for kidney transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene (TNF) polymorphisms on kidney graft survival after transplantation.MethodsWe performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function and death-censored kidney allograft survival in 1271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.ResultsThe G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of immediate graft loss (odds ratio: 2.05; 95%-CI: 1.06–3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05–2.19, P = 0.028).DiscussionIn conclusion, kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.

The Association of TNF-α Promoter Polymorphisms with Genetic Susceptibility to Cervical Cancer in a Chinese Han Population

BackgroundThe tumour necrosis factor-α (TNF-α) gene plays an important role in the host immune response, which will influence the development and clearance of cancer. Polymorphism of the TNF-α promoter region is considered to influence its transcription and be a risk factor for tumorigenesis. In the current study, we evaluated the role of TNF-α promoter region polymorphisms in susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC).MethodsA total of 2732 subjects, including 1173 healthy controls, 579 patients with CIN and 980 patients with CC in a Chinese Han population, were selected for the current study. Five SNPs in the TNF-α promoter, rs1799964 (−1031 C>T), rs1800630 (−863 A>C), rs1799724 (−857 C>T), rs1800629 (−308 A>G) and rs361525 (−238 A>G), were selected and genotyped using TaqMan Assays. The association of these SNPs with CIN and cervical cancer was evaluated among healthy controls, CIN and CC patients.ResultsThe frequency distribution of rs1800629 and rs361525 alleles was significantly different between the CC group and the control group (P=0.009 and P=0.002). The rs1800629 A allele was found to be a protective factor for CC (OR=0.72; 95% CI=0.56–0.92). The rs361525 A allele was found to be a risk factor for CC (OR=1.69; 95% CI=1.21–2.38). After pathological subtyping of CC, the allele distribution of rs1800629 and rs361525 were both significantly different between the cervical squamous cell carcinoma and control groups (P=0.002 and P<0.001). The rs1800629 A allele was protective factor for cervical squamous cell carcinoma (OR=0.66; 95% CI=0.50–0.86). The rs361525 A allele was a risk factor for cervical squamous cell carcinoma (OR=1.87; 95% CI=1.32–2.65). Moreover, the genotypic frequency of rs361525 was significantly different between cervical cancer stage I and stage II (P=0.003).ConclusionThe rs1800629 and rs361525 in the TNF-α promoter are associated with susceptibility to CC in the Chinese Han population.

Association of Tumor Necrosis Factor-α Gene Promoter Polymorphisms with Periodontitisin Type II Diabetic Syrian Population

Association of Tumor Necrosis Factor-α Gene Promoter Polymorphisms with Periodontitisin Type II Diabetic Syrian Population

Dietary supplementation of Solanum aethiopicum and Solanecio biafrae leaves alters stress and immune responses, antioxidant status, and meat quality in broilers raised in a hot-dry environment

ABSTRACT 1. This study investigated the influence of dietary supplementation of Solanum aethiopicum and Solanecio biafrae leaves, which have nutraceutical properties, on stress response, cytokine expression, antioxidant status, blood chemistry, abdominal fat and meat quality in broilers reared in a hot, dry environment. 2. One day old, Ross 308 chicks (n = 350) were randomly allotted to basal diets containing either no supplement (D1); 2.5 g/kg Solanum aethiopicum leaf (SAL; D2); 5 g/kg SAL (D3); 2.5 g/kg Solanecio biafrae leaf (SBL; D4); or 5 g/kg SBL (D5) for 42 d. Birds were reared at 34 ± 2°C and 40–50% relative humidity for 6 h/d from 22–42 d. Each dietary group was replicated in seven pens containing 10 chicks. 3. In the period 1–21 d, body weight gain, feed efficiency and feed intake were not influenced by diet. At 22–42 and 1–42 d, birds supplemented with SAL and SBL had higher (P < 0.05) body weight gain and feed efficiency than the D1 birds. Cloaca temperature, carcase cuts and relative organ weight did not differ between diets. The D3 birds had higher (P < 0.05) erythrocytes and haemoglobin compared with other birds. Dietary supplements reduced (P < 0.05) mortality, abdominal fat, serum total cholesterol, corticosterone, glucose and blood aspartate aminotransferase levels. 4. The treatments up-regulated (P < 0.05) splenic intelukin-10, and down-regulated (P < 0.05) tumour necrosis factor-α and interleukin-1β genes. A dose-dependent improvement (P < 0.05) in antioxidant enzyme activities and total antioxidant capacity of serum and breast muscle were found in the supplemented birds. The breast meat of the supplemented birds had lower (P < 0.05) carbonyl and malondialdehyde contents, and higher (P < 0.05) water holding capacity and redness compared with the non-supplemented meat. 5. These results illustrated that supplementation with either 5 g/kg SAL or 5 g/kg SBL attenuated the deleterious effects of heat stress in broiler chickens.

Human adrenomedullin and its binding protein attenuate tissue injury and inflammation following hepatic ischemia reperfusion in rabbits

BackgroundLiver injury caused by ischemia reperfusion (I/R) during surgical procedures, such as liver resection or liver transplantation, is a major cause of liver damage and graft failure. The current method of treatment is mostly preventative (i.e., ischemic preconditioning). While a number of pharmacological modalities have been studied to reduce hepatic I/R injury, none have been entirely successful. It has been demonstrated that the administration of adrenomedullin (AM) in combination with AM-binding protein (AM/AMBP-1) exerts significant protective effects in various pathological conditions. In an effort to develop AM/AMBP-1 as a novel therapeutic for hepatic I/R injury, the present study examined the effect of a low dose of human AM, which does not induce hypotension, in combination with human AMBP-1 in a rabbit model of hepatic I/R (i.e., non-rodent species). MethodsIschemia of 70% of the liver was induced by placing a microvascular clip across the hilum of the left and median lobes for 60 min. The clip was then removed to commence reperfusion. At 15 min following clip removal (i.e., reperfusion), human AM/AMBP-1 was administered intravenously via the ear marginal vein continuously for 30 min. At 20 h, blood and tissue samples were collected for various measurements. ResultsThe serum levels of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and lactate dehydrogenase, were elevated following hepatic I/R. The administration of AM/AMBP-1 significantly decreased these levels by 58, 44, 41%, respectively. Hepatic I/R increased the direct and total bilirubin levels, whereas treatment with human AM/AMBP-1 decreased these levels by 60% and 69%, respectively. Treatment with AM/AMBP-1 also inhibited interleukin-6 gene expression by 95%. There were no changes in tumor necrosis factor-α (TNF-α) gene expression and myeloperoxidase activity (MPO), lactate and Suzuki scores after treatment. The treatment, however, reduced apoptosis post-hepatic I/R in the ischemic portion of the liver. ConclusionAdditional experiments with AM and AMBP-1 alone are needed to completely interpret the experimental results in this non-rodent species of hepatic I/R injury. The present study suggests that human AM/AMBP-1 may be developed as a novel therapeutic to attenuate hepatic I/R associated inflammation and liver injury.